Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-26T12:57:25.205Z Has data issue: false hasContentIssue false
  • English
  • Français

Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation

Published online by Cambridge University Press:  11 November 2019

Carl G. Gahmberg Open the ORCID record for Carl G. Gahmberg [Opens in a new window] ,
Mikaela Grönholm ,
Sudarrshan Madhavan ,
Farhana Jahan ,
Esa Mikkola ,
Larisa Viazmina  and
Erkki Koivunen
Carl G. Gahmberg*
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Mikaela Grönholm
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Sudarrshan Madhavan
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Farhana Jahan
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Esa Mikkola
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Larisa Viazmina
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
Erkki Koivunen
Affiliation:
Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9 C, 00014 Helsinki, Finland
*
Author for correspondence: C. G. Gahmberg, Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight β-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.

Keywords

Cell adhesionintegrinleukocyteLFA-1phosphorylation
Type
Invited Review
Information
Quarterly Reviews of Biophysics , Volume 52 , 2019 , e10
Copyright
Copyright © Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abram, CL and Lowell, CA (2009) The ins and outs of leukocyte integrin signaling. Annual Review of Immunology 27, 339–362.Google Scholar
Alon, R and Feigelson, SW (2012) Chemokine-triggered leukocyte arrest: force-regulated bi-directional integrin activation in quantal adhesive contacts. Current Opinion of Cell Biology 24, 670–676.Google Scholar
Altieri, DC, Stamnes, SJ and Gahmberg, CG (1992) Regulated Ca++ signalling through leukocyte CD11b/CD18 integrin. Biochemical Journal 288, 465–473.Google Scholar
Andersson, LC and Gahmberg, CG (1978) Surface glycoproteins of human white blood cells. Blood 52, 57–67.Google Scholar
Anthis, NJ and Campbell, ID (2011) The tail of integrin activation. Trends in Biochemical Sciences 36, 191–198.Google Scholar
Arnaout, MA, Spits, H, Terhorst, C, Pitt, J and Todd, RF (1984) Deficiency of a leukocyte surface glycoprotein (LFA-1) in 2 patients with MO1 deficiency – effects of cell activation on Mo1 LFA-1 surface expression in normal and deficient leukocytes. Journal of Clinical Investigation 74, 1291–1300.Google Scholar
Arnaout, MA, Mahalingam, B and Xiong, JP (2005) Integrin structure, allostery, and bidirectional signaling. Annual Review of Cell and Developmental Biology 21, 381–410.Google Scholar
Asada, M, Furukawa, K, Kantor, C, Gahmberg, CG and Kobata, A (1991) Structural study of the sugar chains of human leukocyte cell adhesion molecules CD11/CD18. Biochemistry 30, 1561–1571.Google Scholar
Bachmann, M, Kukkurainen, S, Hytönen, VP and Wehrle-Haller, B (2019) Cell adhesion by integrins. Physiological Reviews 99, 1655–1699.Google Scholar
Bailly, P, Tontti, E, Hermand, P, Cartron, JP and Gahmberg, CG (1995) The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. European Journal of Immunology 25, 3316–3320.Google Scholar
Bennett, JS (2015) A little bit of kindlin goes a long way. Blood 126, 2535–2536.Google Scholar
Bialkowska, K, Byzova, TV and Plow, EF (2015) Site-specific phosphorylation of kindlin-3 protein regulates its capacity to control cellular responses mediated by integrin αIIbβ3. Journal of Biological Chemistry 290, 6226–6242.Google Scholar
Bivona, TG, Wiener, HH, Ahearn, IM, Silletti, J, Chiu, VK and Philips, MR (2004) Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. Journal of Cell Biology 164, 461–470.Google Scholar
Bledzka, K, Bialkowska, K, Sossey-Alaoui, K, Vaynberg, J, Pluskota, E, Qin, J and Plow, EJ (2016) Kindlin-2 directly binds actin and regulates integrin outside-in signaling. Journal of Cell Biology 213, 97–108.Google Scholar
Bleijs, DA, van Duijnhoven, GCF, van Vliet, SJ, Thijssen, JPH, Figdor, CG and van Kooyk, Y (2001) A single amino acid in the cytoplasmic domain of the β2 integrin lymphocyte function-associated antigen-1 regulates avidity-dependent inside-out signaling. Journal of Biological Chemistry 276, 10338–10346.Google Scholar
Blystone, SD, Slater, SE, Williams, MP, Crow, MT and Brown, EJ (1999) A molecular mechanism of integrin crosstalk: αVβ3 suppression of calcium/calmodulin-dependent protein kinase II regulates α5β1 function. Journal of Cell Biology 145, 889–897.Google Scholar
Böttcher, RT, Veelders, M, Rombaut, P, Faix, J, Theodosiou, M, Stradal, TE, Rottner, K, Zent, R, Herzog, F and Fässler, R (2017) Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading. Journal of Cell Biology 216, 3785–3798.Google Scholar
Bromberger, T, Klapproth, S, Rohwedder, I, Zhu, L, Mittmann, L, Reichel, CA, Sperandio, M, Qin, J and Moser, M (2018) Direct Rap1/talin interaction regulates platelet and neutrophil integrin activity in mice. Blood 132, 2754–2762.Google Scholar
Bromley, SK, Burack, WR, Johnson, KG, Somersalo, K, Sims, TN, Sumen, C, Davis, MM, Shaw, AS, Allen, PM and Dustin, ML (2001) The immunological synapse. Annual Review of Immunology 19, 375–396.Google Scholar
Buchbinder, EI and Desai, A (2016) CTLA-4 and PD-1 pathways. Similarities, differences and implications of their inhibition. American Journal of Clinical Oncology 39, 98–106.Google Scholar
Buffone, A, Anderson, NR and Hammer, DA (2018) Migration against the direction of flow is LFA-1-dependent in human hematopoietic stem and progenitor cells. Journal of Cell Science 131, jcs205575.Google Scholar
Burridge, K and Connell, LA (1983) New protein of adhesion plaques and ruffling membranes. Journal of Cell Biology 97, 359–367.Google Scholar
Buyon, JP, Slade, SG, Reibman, J, Abramson, JB, Philips, MR, Weissmann, G and Winchester, R (1990) Constitutive and induced phosphorylation of the α- and β-chains of the CD11/CD18 leukocyte integrin family. Journal of Immunology 144, 191–197.Google Scholar
Byron, A, Humphries, JD, Bass, MD, Knight, D and Humphries, MJ (2011) Proteomic analysis of integrin adhesion complexes. Science Signaling 4, 167 pt2.Google Scholar
Calderwood, DA (2015) The Rap1-RIAM pathway prefers β2 integrins. Blood 126, 2658–2659.Google Scholar
Calderwood, DA, Zent, R, Grant, R, Rees, DJ, Hynes, RO and Ginsberg, MH (1999) The talin head domain binds to integrin-β subunit cytoplasmic tails and regulates integrin activation. Journal of Biological Chemistry 274, 28071–28074.Google Scholar
Calderwood, DA, Campbell, ID and Critchley, DR (2013) Talins and kindlins: partners in integrin-mediated adhesion. Nature Reviews Molecular Cell Biology 14, 503–517.Google Scholar
Campadelli-Fiume, G, Collins-McMillen, D, Gianni, T and Yurochko, AD (2016) Integrins as herpesvirus receptors and mediators of the host signalosome. Annual Review of Virology 3, 215–236.Google Scholar
Campbell, ID (2013) Characterization of 14-3-3-ζ interactions with integrin tails. Journal of Molecular Biology 425, 3060–3072.Google Scholar
Carragher, NO, Levkau, B, Ross, R and Raines, EW (1999) Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. Journal of Cell Biology 147, 619–630.Google Scholar
Castagna, M, Takai, Y, Kaibuchi, K, Sano, K, Kikkawa, U and Nishizuka, Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein-kinase by tumor-promoting phorbol esters. Journal of Biological Chemistry 257, 7847–7851.Google Scholar
Chang, DD, Wong, C, Smith, H and Liu, J (1997) ICAP-1, a novel β1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of β1 integrin. Journal of Cell Biology 138, 1149–1157.Google Scholar
Chang, VT, Fernandes, RA, Ganzinger, KA, Lee, SF, Siebold, C, McColl, J, Jönsson, P, Palayret, M, Harlos, K, Coles, CH, Jones, EY, Lui, Y, Huang, E, Gilbert, RJC, Klenerman, D, Aricescu, AR and Davis, SJ (2016) Initiation of T cell signaling by CD45 segregation at ‘close contacts’. Nature Immunology 17, 574–582.Google Scholar
Chang, Y-C, Su, W, Cho, E-A, Zhang, H, Huang, Q, Philips, MR and Wu, J (2019) Molecular basis for autoinhibition of RIAM regulated by FAK in integrin activation. Proceedings of the National Academy of Sciences of the USA 116, 3524–3529.Google Scholar
Chatila, TA, Geha, RS and Arnaout, MA (1989) Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules. Journal of Cell Biology 109, 3435–3444.Google Scholar
Chatterjee, D, Zhiping, LL, Tan, S-M and Bhattacharjya, S (2016) Interaction analyses of the integrin β2 cytoplasmic tail with the F3 FERM domain of talin and 14-3-3ζ reveal a ternary complex with phosphorylated tail. Journal of Molecular Biology 428, 4129–4142.Google Scholar
Chatterjee, D, D'Souza, A, Zhang, Y, Bin, W, Tan, S-M and Bhattacharjya, S (2018 a) Interaction analyses of 14-3-3ζ, Dok1, and phosphorylated integrin β cytoplasmic tails reveal a bi-molecular switch in integrin regulation. Journal of Molecular Biology 430, 4419–4430.Google Scholar
Chatterjee, D, Zhiping, LL, Tan, S-M and Bhattacharjya, S (2018 b) NMR structure, dynamics and interactions of the integrin β2 cytoplasmic tail with filamin domain IgFLNa21. Scientific Reports 8, 5490.Google Scholar
Chen, C and Sheppard, D (2007) Identification and molecular characterization of multiple phenotypes in integrin knockout mice. Methods in Enzymology 426, 291–305.Google Scholar
Chen, X, Xie, C, Nishida, N, Li, Z, Walz, T and Springer, TA (2010) Requirement of open headpiece conformation for activation of leukocyte integrin αXβ2. Proceedings of the National Academy of Sciences of the USA 107, 14727–14732.Google Scholar
Chen, X, Yu, YM, Mi, LZ, Waltz, T and Springer, TA (2012) Molecular basis for complement recognition by integrin alpha(X) beta (2). Proceedings of the National Academy of Sciences of the USA 109, 4586–4591.Google Scholar
Chigaev, A, Waller, A, Amit, O and Sklar, LA (2008) Galphas-coupled receptor signaling actively down-regulates alpha4beta1-integrin affinity: a possible mechanism for cell-deadhesion. BMC Immunology 9, 26.Google Scholar
Chigaev, A, Smagley, Y and Sklar, LA (2011) Nitric oxide/cGMP pathway signaling actively down-regulates α4β1-integrin affinity: an unexpected mechanism for inducing cell de-adhesion. BMC Immunology 12, 28.Google Scholar
Chigaev, A, Smagley, Y and Sklar, LA (2014) Carbon monoxide down-regulates α4β1 integrin-specific ligand binding and cell adhesion: a possible mechanism for cell mobilization. BMC Immunology 15, 55.Google Scholar
Chinthalapudi, K, Rangarajan, ES and Izard, T (2018) The interaction of talin with the cell membrane is essential for integrin activation and focal adhesion formation. Proceedings of the National Academy of Sciences of the USA 115, 10339–10344.Google Scholar
Choi, EY, Chavakis, E, Czabanka, MA, Langer, HF, Fraemohs, L, Economopoulou, M, Kundu, RK, Orlandi, A, Zheng, YY, Prieto, DA, Ballantyne, CM, Constant, SL, Aird, WC, Papayannopoulou, T, Gahmberg, CG, Udey, MC, Vajkoczy, O, Quartermous, T, Dimmeler, S, Weber, C and Chavakis, T (2008 a) Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science 322, 1101–1104.Google Scholar
Choi, EY, Orlova, VV, Fagerholm, SC, Nurmi, SM, Zhang, L, Ballantyne, CM, Gahmberg, CG and Chavakis, T (2008 b) Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins. Blood 111, 3607–3614.Google Scholar
Coppolino, M, Leung-Hagesteijn, C, Dedhar, S and Wilkins, J (1995) Inducible interaction of integrin α2β1 with calreticulin. Dependence on the activation state of the integrin. Journal of Biological Chemistry 270, 23132–23138.Google Scholar
Coppolino, MG, Woodside, MJ, Demaurex, N, Grinstein, S, St-Arnaud, R and Dedhar, S (1997) Calreticulin is essential for integrin-mediated calcium signalling and adhesion. Nature 386, 843–847.Google Scholar
Corsini, A, Maggi, FM and Catapano, AL (1995) Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacological Research 31, 9–27.Google Scholar
Courtney, AH, Amacher, JF, Kadlecek, TA, Mollenauer, MN, Au-Yeung, BB, Kuriyan, J and Weiss, A (2017) A phosphosite within the SH2 domain of Lck regulates its activation by CD45. Molecular Cell 67, 498–511.Google Scholar
Courtney, AH, Lo, W-L and Weiss, A (2018) TCR signaling: mechanisms of initiation and propagation. Trends in Biochemical Sciences 43, 108–123.Google Scholar
Critchley, DR (2009) Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annual Review of Biopysics 38, 235–254.Google Scholar
Das, M, Ithychanda, SS, Qin, J and Plow, EF (2011) Migfilin and filamin as regulators of integrin activation in endothelial cells and neutrophils. PLoS ONE 6, e26355.Google Scholar
Davies, JC, Tamaddon-Jahromi, S, Jannoo, R and Kanamalapudi, V (2014) Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK 1/2. Biochemical Pharmacology 15, 651–660.Google Scholar
Diamond, MS, Staunton, DE, Marlin, SD and Springer, TA (1991) Binding of the integrin Mac-1 (CD11B/CD18) to the 3rd immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 65, 961–971.Google Scholar
Dimitrov, S, Lange, T, Gouttefangeas, C, Jensen, ATR, Szczepanski, M, Lehnnolz, J, Soekadar, S, Rammensee, H-G, Born, J and Besedovsky, L (2019) Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells. Journal of Experimental Medicine 216, 517–526.Google Scholar
Dominguez, GA, Anderson, NR and Hammer, DA (2015) The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged. Integrative Biology 7, 345–355.Google Scholar
Dong, XC, Mi, LZ, Zhu, JH, Wang, W, Hu, O, Luo, BH and Springer, TA (2012) Alpha(v)beta(3) integrin crystal structures and their functional implications. Biochemistry 51, 8814–8828.Google Scholar
Downey-Biechler, C, Craig, DH, More, SK and Basson, MD (2019) Inside-out signaling through FAK-integrin axis may regulate circulating cancer cell metastatic adhesion. Proceedings of the National Academy of Sciences of the USA 116, 19795–19796.Google Scholar
Dransfield, I, Cabanas, C, Craig, A and Hogg, N (1992) Divalent-cation regulation of the function of the leukocyte integrin LFA-1. Journal of Cell Biology 116, 219–226.Google Scholar
Durrant, TN, van den Bosch, M and Hers, I (2017) Integrin αIIbβ3 outside-in signaling. Blood 130, 1607–1619.Google Scholar
Dutta, D, Barr, VA, Akpan, I, Mittelstadt, PR, Singha, LI, Samelson, LE and Ashwell, JD (2017) Recruitment of calcineurin to the TCR positively regulates T cell function. Nature Immunology 18, 196–204.Google Scholar
Fagerholm, S, Prescott, A, Cohen, P and Gahmberg, CG (2001) An essential role for calmodulin in regulating human T cell aggregation. FEBS Letters 491, 131–136.Google Scholar
Fagerholm, S, Hilden, TJ and Gahmberg, CG (2002 a) Lck tyrosine kinase is important for activation of the CD11a/CD18 integrins in human T lymphocytes. European Journal of Immunology 32, 1670–1678.Google Scholar
Fagerholm, S, Morrice, N, Gahmberg, CG and Cohen, P (2002 b) Phosphorylation of the cytoplasmic domain of the integrin CD18 chain by protein kinase C isoforms in leukocytes. Journal of Biological Chemistry 277, 1728–1738.Google Scholar
Fagerholm, SC, Hilden, TJ, Nurmi, SM and Gahmberg, CG (2005) Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and –independent mechanisms. Journal of Cell Biology 171, 705–715.Google Scholar
Fagerholm, SC, Varis, M, Stefanidakis, M, Hilden, TJ and Gahmberg, CG (2006) α-chain phosphorylation of the human leukocyte CD11b/CD18 (Mac-1) integrin is pivotal for integrin activation to bind ICAMs and leukocyte extravasation in vivo. Blood 108, 3379–3386.Google Scholar
Fagerholm, SC, Guenther, C, Asens, ML, Savinko, T and Uotila, LM (2019) Beta2-integrins and interacting proteins in leukocyte trafficking, immune suppression, and immunodeficiency disease. Frontiers in Immunology 10, article 254.Google Scholar
Fong, KP, Zhu, H, Span, LM, Moore, DT, Yoon, K, Tamura, R, Yin, H, DeGrado, WF and Bennett, JS (2016) Directly activating the integrin αIIbβ3 initiates outside-in signaling by causing αIIbβ3 clustering. Journal of Biological Chemistry 291, 11706–11716.Google Scholar
Franco, SJ and Huttenlocher, A (2005) Regulating cell migration: calpains make the cut. Journal of Cell Science 118, 829–838.Google Scholar
Franco, SJ, Rodgers, MA, Perrin, BJ, Han, J, Bennin, DA, Critchley, DR and Huttenlocher, A (2004) Calpain-mediated proteolysis of talin regulated adhesion dynamics. Nature Cell Biology 6, 977–983.Google Scholar
Frenette, PS (2001) Locking a leukocyte integrin with statins. The New England Journal of Medicine 345, 1419–1421.Google Scholar
Gahmberg, CG (1997) Leukocyte adhesion. CD11/CD18 integrins and intercellular adhesion molecules. Current Opinion in Cell Biology 9, 643–650.Google Scholar
Gahmberg, CG and Hakomori, S (1973) Altered growth behavior of malignant cells associated with changes in externally labeled glycoprotein and glycolipid. Proceedings of the National Academy of Sciences of the USA 70, 3329–3333.Google Scholar
Gahmberg, CG, Häyry, P and Andersson, LC (1976) Characterization of surface glycoproteins of mouse lymphoid cells. Journal of Cell Biology 68, 642–653.Google Scholar
Gahmberg, CG, Tolvanen, M and Kotovuori, P (1997) Leukocyte adhesion. Structure and function of human leukocyte β2-integrins and their cellular ligands. European Journal of Biochemistry 245, 215–232.Google Scholar
Gahmberg, CG, Tian, L, Ning, L and Nyman-Huttunen, H (2008) ICAM-5 – a novel two-facetted adhesion molecule in the mammalian brain. Immunology Letters 117, 131–135.Google Scholar
Gahmberg, CG, Fagerholm, SC, Nurmi, SM, Chavakis, T, Marchesan, S and Grönholm, M (2009) Regulation of integrin activity and signalling. Biochimica et Biophysica Acta 1790, 431–444.Google Scholar
Gailit, J and Ruoslahti, E (1988) Regulation of the fibronectin receptor affinity by divalent-cations. Journal of Biological Chemistry 263, 12927–12932.Google Scholar
Gao, J, Bao, Y, Ge, S, Sun, P, Sun, J, Liu, J, Chen, F, Han, L, Cao, Z, Qin, J, White, GC, Xu, Z and Ma, Y-Q (2019) Sharpin suppresses β1-integrin activation by complexing with the β1 tail and kindlin-1. Cell Communication and Signaling. doi: doi.org/10.1186/s12964-019-0407-6.Google Scholar
Gatta, L, Calviello, G, di Nicuolo, F, Pace, L, Ubaldi, V, Doria, G and Pioli, C (2002) Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation. Immunology 107, 209–2016.Google Scholar
Gbarah, A, Gahmberg, CG, Ofek, I, Jacobi, U and Sharon, N (1991) Identification of the leukocyte adhesion molecules CD11 and CD18 as receptors for type 1 fimbriated (Mannose specific) Escherichia coli. Infection and Immunity 59, 4524–4530.Google Scholar
Geng, X, Tang, R-H, Law, SKA and Tan, S-M (2005) Integrin CD11a cytoplasmic tail interacts with the CD45 membrane-proximal protein tyrosine phosphatase domain 1. Immunology 115, 347–357.Google Scholar
Ghosh, S, Chackerian, AA, Parker, CM, Ballantyne, CM and Behar, SM (2006) The LFA-1 adhesion molecule is required for protective immunity during pulmonary Mycobacterium tuberculosis infection. Journal of Immunology 176, 4914–4922.Google Scholar
Giancotti, FG and Ruoslahti, E (1999) Integrin signaling. Science 285, 1028–1032.Google Scholar
Gingras, AR, Lagarrique, F, Cuevas, MN, Valadez, AJ, Zorovich, M, McLaughlin, W, Lopez-Ramirez, MA, Seban, N, Ley, K, Kiosses, WB and Ginsberg, MH (2019) Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem. Journal of Cell Biology. doi: doi.org/10.1083/jcb.201810061.Google Scholar
Glading, A, Lauffenburger, D and Wells, A (2002) Cutting to the chase: calpain proteases in cell motility. Trends in Cell Biology 12, 46–54.Google Scholar
Gong, Y, Zhang, Y, Feng, S, Liu, X, Lu, S and Long, M (2017) Dynamic distributions of P- and E-selectins to beta2-integrin-induced neutrophil transmigration. FASEB Journal 31, 212–223.Google Scholar
Gonzales, AM, Claiborne, J and Jones, CR (2008) Integrin cross-talk in endothelial cells is regulated by protein kinase A and protein phosphatase 1. Journal of Biological Chemistry 283, 31849–31860.Google Scholar
Goult, BT and Schwartz, MA (2018) Talin as a mechanosensitive signaling hub. Journal of Cell Biology 217, 3776–3784.Google Scholar
Grakoui, A, Bromley, SK, Sumen, C, Davis, MM, Shaw, AS, Allen, PM and Dustin, ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227.Google Scholar
Grönholm, M, Jahan, F, Marchesan, S, Karvonen, U, Aatonen, M, Narumanchi, S and Gahmberg, CG (2011) TCR-induced activation of LFA-1 involves signaling through Tiam1. Journal of Immunology 187, 3613–3619.Google Scholar
Grönholm, M, Jahan, F, Bryushkova, EA, Madhavan, S, Aglialoro, F, Hinojosa, LS, Uotila, LM and Gahmberg, CG (2016) LFA-1 integrin antibodies inhibit leukocyte α4β1-mediated adhesion by intracellular signaling. Blood 128, 1270–1281.Google Scholar
Gupta, S, Chit, JC-Y, Feng, C, Bhunia, A, Tan, S-M and Bhattacharjya, S (2015) An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding. Scientific Reports 5, 11630.Google Scholar
Han, DC, Rodriguez, LG and Guan, JL (2001) Identification of a novel interaction between integrin β1 and 14-3-3β. Oncogene 20, 346–357.Google Scholar
Han, J, Rose, DM, Woodside, DG, Goldfinger, LE and Ginsberg, MH (2003) Integrin α4β1-dependent T cell migration requires both phosphorylation and dephosphorylation of the α4 cytoplasmic domain to regulate the reversible binding of paxillin. Journal of Biological Chemistry 278, 34845–34853.Google Scholar
Hibbs, ML, Jakes, S, Stacker, SA, Wallace, RW and Springer, TA (1991) The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 β subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. Journal of Experimental Medicine 174, 1227–1238.Google Scholar
Hilden, TJ, Valmu, L, Kärkkäinen, S and Gahmberg, CG (2003) Threonine phosphorylation sites in the β2 and β7 leukocyte integrin polypeptides. Journal of Immunology 170, 4170–4177.Google Scholar
Hogg, N, Patzak, I and Willenbrock, F (2011) The insider's guide to leukocyte integrin signaling and function. Nature Reviews Immunology 11, 416–426.Google Scholar
Hu, P and Luo, B-H (2013) Integrin bi-directional signaling across the plasma membrane. Journal of Cellular Physiology 228, 306–312.Google Scholar
Hughes, PE, Diaz-Gonzales, F, Leong, L, Wu, C, McDonald, JA, Shattil, SJ and Ginsberg, MH (1996) Breaking the integrin hinge. A defined structural constraint regulates integrin signaling. Journal of Biological Chemistry 271, 6571–6574.Google Scholar
Humphries, JD, Byron, A and Humphries, MJ (2006) Integrin ligands. Journal of Cell Science 119, 3901–3903.Google Scholar
Huse, M (2017) Mechanical forces in the immune system. Nature Reviews Immunology 17, 679–690.Google Scholar
Huttenlocher, A and Horwitz, AR (2011) Integrins in cell migration. Cold Spring Harbor Perspectives in Biology 3, a005074.Google Scholar
Hynes, RO (1973) Alteration of cell-surface proteins by viral transformation and by proteolysis. Proceedings of the National Academy of Sciences of the USA 70, 3170–3174.Google Scholar
Hynes, RO (1987) Integrins: a family of cell surface receptors. Cell 48, 549–554.Google Scholar
Hynes, RO (1992) Integrins – versatility, modulation, and signaling in cell-adhesion. Cell 69, 11–25.Google Scholar
Hynes, RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687.Google Scholar
Hynes, RO and Yamada, KM (1982) Fibronectins-multifunctional modular glycoproteins. Journal of Cell Biology 95, 369–377.Google Scholar
Ithychanda, SS, Fang, X, Mohan, ML, Zhu, L, Tirupula, KC, Prasad, SVN, Wang, Y-X, Karnik, SS and Qin, J (2015) A mechanism of global shape-dependent recognition and phosphorylation of filamin by protein kinase A. Journal of Biological Chemistry 290, 8527–8538.Google Scholar
Jackson, T, Sheppard, D, Denyer, M, Blakemore, W and King, AMQ (2000) The epithelial integrin αvβ6 is a receptor for foot-and-mouth disease virus. Journal of Virology 74, 4949–4956.Google Scholar
Jahan, F, Madhavan, S, Rolova, T, Viazmina, L, Grönholm, M and Gahmberg, CG (2018) Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion. Journal of Biological Chemistry 293, 12318–12330.Google Scholar
Jenkins, AL, Nannizzi-Alaimo, L, Silver, D, Sellers, JR, Ginsberg, MH, Law, DA and Phillips, DR (1998) Tyrosine phosphorylation of the beta3 cytoplasmic domain mediates integrin-cytoskeletal interactions. Journal of Biological Chemistry 273, 13878–13885.Google Scholar
Johnson, KG, Bromley, SK, Dustin, ML and Thomas, ML (2000) A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation. Proceedings of the National Academy of Sciences of the USA 97, 10138–10143.Google Scholar
Kammerer, P, Aretz, J and Fässler, R (2017) Lucky kindlin: a cloverleaf at the integrin tail. Proceedings of the National Academy of Sciences of the USA 114, 9234–9236.Google Scholar
Kanwar, S, Smith, CW, Shardonofsky, FR and Burns, AR (2001) The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice. American Journal of Respiratory Cell and Molecular Biology 25, 170–177.Google Scholar
Kasirer-Friede, A, Tjahjono, W, Eto, K and Shattil, SJ (2019) SHARPIN at the nexus of integrin, immune, and inflammatory signaling in human platelets. Proceedings of the National Academy of Sciences of the USA 216, 4983–4988.Google Scholar
Katagiri, K, Maeda, A, Shimonaka, M and Kinashi, T (2003) RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nature Immunology 4, 741–748.Google Scholar
Katagiri, K, Imamura, M and Kinashi, T (2006) Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nature Immunology 7, 919–928.Google Scholar
Kiema, T, Lad, Y, Jiang, P, Oxley, CL, Baldassarre, M, Wegener, KL, Campbell, ID, Ylänne, J and Calderwood, DA (2006) The molecular basis of filamin binding to integrins and competition with talin. Molecular Cell 21, 337–347.Google Scholar
Kim, M, Carman, CV and Springer, TA (2003) Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720–1725.Google Scholar
Kim, C, Lau, T-L, Ulmer, TS and Ginsberg, MH (2009) Interactions of platelet integrin αIIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation. Blood 113, 4747–4753.Google Scholar
Kim, CK, Ye, F, Hu, X and Ginsberg, MH (2012) Talin activates integrins by altering the topology of the β transmembrane domain. Journal of Cell Biology 197, 605–611.Google Scholar
Kirk, RI, Sanderson, MR and Lerea, KM (2000) Threonine phosphorylation of the β3 integrin cytoplasmic tail, at a site recognized by PDK1 and Akt/PKB in vitro, regulates Shc binding. Journal of Biological Chemistry 275, 30901–30906.Google Scholar
Klapholz, B and Brown, NH (2017) Talin-the master of integrin adhesions. Journal of Cell Science 130, 2435–2446.Google Scholar
Klapproth, S, Moretti, FA, Zeiler, M, Ruppert, R, Breithaupt, U, Mueller, S, Haas, R, Mann, M, Sperandio, M, Fässler, R and Moser, M (2015 a) Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice. Blood 126, 2592–2600.Google Scholar
Klapproth, S, Sperandio, M, Pinheiro, EM, Prunster, M, Soehnlein, O, Gertler, FB, Fässler, R and Moser, M (2015 b) Loss of the Rap1 effector RIAM results in leukocyte adhesion deficiency due to impaired β2 integrin function in mice. Blood 126, 2704–2712.Google Scholar
Klapproth, S, Bromberger, T, Turk, C, Kruger, M and Moser, M (2019) A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability. Journal of Cell Biology 218, 3436.Google Scholar
Knight, CG, Morton, LF, Peachey, AR, Tuckwell, DS, Farndale, RW and Barnes, MJ (2000) The collagen-binding A-domains of integrins α1β1 and α2β1 recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens. Journal of Biological Chemistry 275, 35–40.Google Scholar
Koivunen, E, Ranta, TM, Annila, A, Taube, S, Uppala, A, Jokinen, M, van Willigen, G, Ihanus, E and Gahmberg, CG (2001) Inhibition of β2 integrin-mediated leukocyte cell adhesion by leucine-leucine-glycine motif-containing peptides. Journal of Cell Biology 153, 905–916.Google Scholar
Kolanus, W (2007) Guanine nucleotide exchange factors of the cytohesin family and their roles in signal transduction. Immunological Reviews 218, 102–113.Google Scholar
Kondo, N, Ueda, Y, Kita, T, Ozawa, M, Tomiyama, T, Yasuda, K, Lim, D-S and Kinashi, T (2017) NDR1-dependent regulation of kindlin-3 controls high-affinity LFA-1 binding and immune synapse organization. Molecular and Cellular Biology 37, e00424–16.Google Scholar
Kong, K-F and Altman, A (2013) In and out of the bull's eye: protein kinase Cs in the immunological synapse. Trends in Immunology 34, 234–242.Google Scholar
Kotovuori, P, Tontti, E, Pigott, R, Shepherd, M, Kiso, M, Hasegawa, A, Renkonen, R, Nortamo, P, Altieri, DC and Gahmberg, CG (1993) The vascular E-selectin binds to the leukocyte integrins CD11/CD18. Glycobiology 3, 131–136.Google Scholar
Kotovuori, A, Pessa-Morikawa, T, Kotovuori, P, Nortamo, P and Gahmberg, CG (1999) ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity. Journal of Immunology 162, 6613–6620.Google Scholar
Kourtzelis, I, Mitroulis, I, von Renesse, J, Hajishengallis, G and Chavakis, T (2017) From leukocyte recruitment to resolution of inflammation: the cardinal role of integrins. Journal of Leukocyte Biology 102, 677–683.Google Scholar
Krause, K-H and Michalak, M (1997) Calreticulin. Cell 88, 439–443.Google Scholar
Krueger, J, Gottlieb, A, Miller, B, Dedrick, R, Garovoy, M and Walicke, P (2000) Anti-CD11a treatment for psoriasis concurrently increases circulating T-cells and decreases plaque T-cells, consistent with inhibition of cutaneous T-cell trafficking. Journal of Investigative Dermatology 115, 333.Google Scholar
Lagarrique, F, Kim, C and Ginsberg, MH (2016) The Rap1-RIAM-talin axis of integrin activation and blood cell function. Blood 128, 479–487.Google Scholar
Law, DA, DeGuzman, FR, Heiser, P, Ministri-Madrid, K, Killeen, N and Phillips, DR (1999) Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbβ3 signalling and platelet function. Nature 401, 808–811.Google Scholar
Lee, J-O, Rieu, P, Arnaout, MA and Liddington, R (1995) Crystal structure of the A domain from the α subunit of integrin CR3 (CD11b/CD18). Cell 80, 631–638.Google Scholar
Lerea, KM, Cordero, KP, Sakariassen, KS, Kirk, RI and Fried, VA (1999) Phosphorylation sites in the integrin β3 cytoplasmic domain in intact platelets. Journal of Biological Chemistry 274, 1914–1919.Google Scholar
Li, J and Springer, TA (2017 a) Integrin extension enables ultrasensitive regulation by cytoskeletal force. Proceedings of the National Academy of Sciences of the USA 114, 4685–4690.Google Scholar
Li, J and Springer, TA (2017 b) Energy landscape differences among integrins establish the framework for understanding activation. Journal of Cell Biology 217, 397–412.Google Scholar
Li, R, Nortamo, P, Kantor, C, Kovanen, P, Timonen, T and Gahmberg, CG (1993) A leukocyte integrin binding peptide from intercellular adhesion molecule-2 stimulates T cell adhesion and natural killer cell activity. Journal of Biological Chemistry 268, 21474–21477.Google Scholar
Li, Z, Zhang, H, Lundin, L, Thullberg, M, Liu, Y, Wang, Y, Claesson-Welsh, L and Strömblad, S (2010) p21-activated kinase 4 phosphorylation of integrin β5 Ser-759 and Ser-762 regulates cell migration. Journal of Biological Chemistry 285, 23699–23710.Google Scholar
Li, H, Deng, Y, Sun, K, Yang, H, Liu, J, Wang, M, Zhang, Z, Lin, J, Wu, C, Wei, Z and Yu, C (2017) Structural basis of kindlin-mediated integrin recognition and activation. Proceedings of the National Academy of Sciences of the USA 114, 9349–9354.Google Scholar
Lilienthal, J and Chang, DD (1998) Rack1, a receptor for activated protein kinase C, interacts with integrin β subunit. Journal of Biological Chemistry 273, 2379–2383.Google Scholar
Lilja, J, Zacharchenko, T, Georgiadou, M, Jacquemet, G, De Franceschi, N, Peuhu, E, Hamidi, H, Pouwels, J, Martens, V, Nia, FH, Beifuss, M, Boeckers, T, Kreienkamp, H-J, Barsukov, IL and Ivaska, J (2017) SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Nature Cell Biology 19, 292–305.Google Scholar
Lim, CJ, Kain, KH, Tkachenko, E, Goldfinger, LE, Gutierrez, E, Allen, MD, Groisman, A, Zhang, J and Ginsberg, MH (2008) Integrin-mediated protein kinase A activation at the leading edge of migrating cells. Molecular Biology of the Cell 19, 4930–4941.Google Scholar
Lim, J, Hotchin, NA and Caron, E (2011) Ser756 of β2 integrin controls Rap1 activity during inside-out activation of αMβ2. Biochemical Journal 437, 461–467.Google Scholar
Lin, C, Zhang, Y, Zhang, K, Zheng, Y, Lu, L, Chang, H, Yang, H, Yang, Y, Wan, Y, Wang, S, Yuan, M, Yan, Z, Zhang, R, He, Y, Ge, G, Wu, D and Chen, J (2019) Fever promotes T lymphocyte trafficking via a thermal sensory pathway involving heat shock protein 90 and α4 integrins. Immunity 50, 137–151.Google Scholar
Liu, S and Ginsberg, MH (2000) Paxillin binding to a conserved sequence motif in the α4 integrin cytoplasmic domain. Journal of Biological Chemistry 275, 22736–22742.Google Scholar
Liu, J, Das, M, Yang, J, Ithychanda, SS, Yakubenko, V, Plow, EF and Qin, J (2015 a) Structural mechanism of integrin inactivation by filamin. Nature Structural & Molecular Biology 22, 383–391.Google Scholar
Liu, J, Wang, Z, Thinn, AMM, Ma, Y-Q and Zhu, J (2015 b) The dual structural roles of the membrane distal region of the α-integrin cytoplasmic tail during integrin inside-out activation. Journal of Cell Science 128, 1718–1731.Google Scholar
Lu, L, Lin, C, Yan, Z, Wang, S, Zhang, Y, Wang, S, Wang, J, Liu, C and Chen, J (2016) Kindlin-3 is essential for the resting α4β1 integrin-mediated firm cell adhesion under shear flow conditions. Journal of Biological Chemistry 291, 10363–10371.Google Scholar
Luo, BH, Carman, CV and Springer, TA (2007) Structural basis of integrin regulation and signaling. Annual Review of Immunology 25, 619–647.Google Scholar
MacKenzie, KR, Prestegard, JH and Engelman, DM (1997) A transmembrane helixdimer, structure and implications. Science 276, 131–133.Google Scholar
Malinin, NL, Zhang, L, Choi, J, Ciocea, A, Razorenova, O, Ma, Y-Q, Podrez, EA, Tosi, M, Lennon, DP, Caplan, AI, Shurin, SB, Plow, EF and Byzova, TV (2009) A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nature Medicine 15, 313–318.Google Scholar
Mitroulis, I, Kang, YY, Gahmberg, CG, Siegert, G, Hajishengallis, G, Chavakis, T and Choi, EY (2014) Developmental endothelial locus-1 attenuates complement-dependent phagocytosis through inhibition of Mac-1 integrin. Journal of Cell Science 129, 1004–1006.Google Scholar
Mitroulis, J, Alexaki, VI, Kourtzelis, J, Ziogas, A, Hajishengallis, G and Chavakis, T (2015) Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease. Pharmacology & Therapeutics 147, 123–135.Google Scholar
Moore, TI, Aaron, J, Chew, T-L and Springer, TA (2018) Measuring integrin conformational change on the cell surface with super-resolution microscopy. Cell Reports 22, 1903–1912.Google Scholar
Morikis, VA, Chase, S, Wun, T, Chaikof, EL, Magnani, JL and Simon, SI (2017) Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow. Blood 130, 2101–2110.Google Scholar
Morrison, VL, MacPherson, M, Savinko, T, Lek, HS, Prescott, A, Fagerholm, SC (2013) The β2 integrin-kindlin-3 interaction is essential for T cell homing but dispensable for T- cell activation in vivo. Blood 122, 1428-1436.Google Scholar
Moser, M, Bauer, M, Schmid, S, Ruppert, R, Schmidt, S, Sixt, M, Wang, H-V, Sperandio, M and Fässler, R (2009 a) Kindlin-3 is required for β2 integrin-mediated leukocyte adhesion to endothelial cells. Nature Medicine 15, 300–305.Google Scholar
Moser, M, Legate, KR, Zent, R and Fässler, R (2009 b) The tail of integrins, talin and kindlins. Science 324, 895–899.Google Scholar
Muslin, AJ, Tanner, JW, Allen, PM and Shaw, AS (1996) Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 84, 889–897.Google Scholar
Mustelin, T, Coggeshall, KM and Altman, A (1989) Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase. Proceedings of the National Academy of Sciences of the USA 86, 6302–6306.Google Scholar
Mustelin, T, Pessa-Morikawa, T, Autero, M, Gassman, M, Gahmberg, CG, Andersson, LC and Burn, P (1992) Regulation of the pp59fyn tyrosine kinase by the CD45 phosphotyrosine phosphatase. European Journal of Immunology 22, 1173–1178.Google Scholar
Needham, EJ, Parker, BL, Burykin, T, James, DE and Humphrey, SJ (2019) Illuminating the dark phosphoproteome. Science Signaling 12, eaau8645.Google Scholar
Newton, AC (1995) Protein kinase C: structure, function, and regulation. Journal of Biological Chemistry 270, 28495–22849.Google Scholar
Newton, AC and Brognard, J (2017) Reversing the paradigm: protein kinase C as a tumor suppressor. Trends in Pharmacological Sciences 38, 438–447.Google Scholar
Nilsson, S, Kaniowska, D, Brakebusch, C, Fässler, R and Johansson, S (2006) Threonine 788 in integrin subunit β1 regulates integrin activation. Experimental Cell Research 312, 844–853.Google Scholar
Nishida, N, Xie, C, Shimaoka, M, Cheng, Y, Walz, T and Springer, TA (2006) Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity 25, 583–594.Google Scholar
Nishizuka, Y (1984) The role of protein kinase-C in cell surface signal transduction and tumor promotion. Nature 308, 693–698.Google Scholar
Nordenfelt, P, Elliott, HL and Springer, TA (2016) Coordinated integrin activation by actin-dependent force during T-cell migration. Nature Communications 7, 13119.Google Scholar
Nortamo, P, Patarroyo, M, Kantor, C, Suopanki, J and Gahmberg, CG (1988) Immunological mapping of the human leukocyte adhesion glycoprotein GP90 (CD18) by monoclonal antibodies. Scandinavian Journal of Immunology 28, 537–546.Google Scholar
Nurmi, SM, Autero, M, Raunio, AK, Gahmberg, CG and Fagerholm, SC (2007) Phosphorylation of the LFA-1 integrin β2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation and stimulation of CD69 expression in human T cells. Journal of Biological Chemistry 282, 968–975.Google Scholar
Nygren, P, Balashova, N, Brown, AC, Kieba, I, Dhingra, A, Boesze-Battaglia, K and Lally, ET (2018) Aggregatibacter actinomycetemcomitans leukotoxin causes activation of lymphocyte function-associated antigen 1. Cellular Microbiology 21. doi: doi.org/10.1111/cmi.12967.Google Scholar
Obergfell, A, Eto, K, Mocsai, A, Buensuceso, C, Moores, SL, Brugge, JS, Lowell, CA and Shattil, SJ (2002) Coordinate interactions of Csk, Src, and Syk kinases with αIIbβ3 initiate integrin signaling to the cytoskeleton. Journal of Cell Biology 157, 265–275.Google Scholar
Okigaki, M, Davis, C, Falasca, M, Harroch, S, Felsenfeld, DP, Sheetz, MP and Schlesinger, J (2003) Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration. Proceedings of the National Academy of Sciences of the USA 100, 10740–10745.Google Scholar
O'Toole, TE, Bialkowska, K, Li, X and Fox, JEB (2011) Tiam1 is recruited to β1-integrin complexes by 14-3-3 ζ where it mediates integrin-induced Rac1 activation and motility. Journal of Cellular Physiology 226, 2965–2978.Google Scholar
Oxley, CL, Anthis, NJ, Lowe, ED, Vakonakis, I, Campbell, ID and Wegener, KL (2008) An integrin phosphorylation switch. The effect of β3 integrin tail phosphorylation on Dok1 and talin binding. Journal of Biological Chemistry 283, 5420–5426.Google Scholar
Parry, RV, Chemnitz, JM, Frauwirth, KA, Lanfranco, AR, Braunstein, I, Kobayashi, SV, Linsley, PS, Thompson, CB and Riley, JL (2005) CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Molecular and Cellular Biology 25, 9543–9553.Google Scholar
Patarroyo, M, Yogeeswaran, G, Biberfeld, P, Klein, E and Klein, G (1982) Morphological-changes, cell-aggregation and cell-membrane alterations caused by phorbol 12,13-dibutyrate in human-blood lymphocytes. International Journal of Cancer 30, 707–717.Google Scholar
Patarroyo, M, Beatty, PG, Fabre, JW and Gahmberg, CG (1985 a) Identification of a cell surface protein complex mediating phorbol ester-induced adhesion (binding) among human mononuclear leukocytes. Scandinavian Journal of Immunology 22, 171–182.Google Scholar
Patarroyo, M, Beatty, PG, Serhan, CN and Gahmberg, CG (1985 b) Identification of a cell surface glycoprotein mediating adhesion in human granulocytes. Scandinavian Journal of Immunology 22, 619–631.Google Scholar
Patarroyo, M, Clark, EA, Prieto, J, Kantor, C and Gahmberg, CG (1987) Identification of a novel adhesion molecule in human leukocytes by monoclonal antibody LB-2. FEBS Letters 210, 127–131.Google Scholar
Pavalko, FM and LaRoche, SM (1993) Activation of human neutrophils induces an interaction between the integrin β2-subunit (CD18) and the actin binding protein α-actinin. Journal of Immunology 151, 3795–3807.Google Scholar
Perez, OD, Mitchell, D, Jager, GC, South, S, Murriel, C, McBride, J, Herzenberg, LA, Kinoshita, S and Nolan, GP (2003) Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1. Nature Immunology 4, 1083–1094.Google Scholar
Petosa, C, Masters, SC, Bankston, LA, Pohl, J, Wang, B, Fu, H and Liddington, RC (1998) 14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove. Journal of Biological Chemistry 273, 16305–16310.Google Scholar
Philipsen, L, Reddycherla, AV, Hartig, R, Gumz, J, Kästle, M, Kritikos, A, Poltorak, MP, Prokazov, Y, Turbin, E, Weber, A, Zuschratter, W, Schraven, B, Simeoni, L and Muller, AJ (2017) De novo phosphorylation and conformational opening of the tyrosine kinase Lck act in concert to initiate T cell receptor signaling. Science Signaling 10, eaaf4736.Google Scholar
Phillips, ML, Nudelman, E, Gaeta, FCA, Perez, M, Singhal, AK, Hakomori, S and Paulson, JC (1990) ELAM-1 mediates cell-adhesion by recognition of a carbohydrate ligand, sialyl-LeX. Science 250, 1130–1132.Google Scholar
Pierschbacher, MD and Ruoslahti, E (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309, 30–33.Google Scholar
Polley, MJ, Phillips, ML, Wayner, E, Nudelman, E, Singhal, AK, Hakomori, S and Paulson, JC (1991) CD62 and endothelial cell-leukocyte adhesion molecule I (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. Proceedings of the National Academy of Sciences of the USA 88, 6224–6228.Google Scholar
Pons, M, Izquierdo, I, Andreu-Carbo, M, Garrido, G, Planaguma, J, Muriel, O, del Pozo, MA, Geli, MI and Aragay, AM (2017) Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling. Journal of Cell Science 130, 490–501.Google Scholar
Porter, JC and Hogg, N (1997) Integrin cross-talk: activation of lymphocyte function-associated antigen-1 on human T cells alters α4β1- and α5β1-mediated function. Journal of Cell Biology 138, 1437–1447.Google Scholar
Pouwels, J, de Franceschi, N, Mattila, E, Potter, C, Sundberg, J, Hogg, N, Gahmberg, CG, Salmi, M and Ivaska, J (2013) SHARPIN regulates uropod detachment in migrating lymphocytes. Cell Reports 5, 619–628.Google Scholar
Puck, A, Hopf, S, Modak, M, Majdic, O, Cejka, P, Blumi, S, Schmetterer, K, Arnold-Schrauf, C, Gerwien, JG, Frederiksen, KS, Thell, E, Leitner, J, Steinberger, P, Aigner, R, Seyerl-Jiresch, M, Zlabinger, GJ and Stöckl, J (2017) The soluble cytoplasmic tail of CD45 (ct-CD45) in human plasma contributes to keep T cells in a quiescent state. European Journal of Immunology 47, 193–205.Google Scholar
Pytela, R, Pierschbacher, MD and Ruoslahti, E (1985) Identification and isolation of a 140-kd cell-surface glycoprotein with properties expected of a fibronectin receptor. Cell 40, 191–198.Google Scholar
Rantala, JK, Pouwels, J, Pellinen, T, Veltel, S, Laasola, P, Mattila, E, Potter, CS, Duffy, T, Sundberg, JP, Kallioniemi, O, Askari, JA, Humphries, MJ, Parsons, M, Salmi, M and Ivaska, J (2011) SHARPIN is an endogenous inhibitor of β1-integrin activation. Nature Cell Biology 13, 1315–1324.Google Scholar
Ratnikov, B, Ptak, C, Han, J, Shabanowitz, J, Hunt, DF and Ginsberg, MH (2005) Talin phosphorylation sites mapped by mass spectrometry. Journal of Cell Science 118, 4921–4923.Google Scholar
Robinson, MK, Andrew, D, Rosen, H, Brown, D, Ortlepp, S, Stephens, P and Butcher, EC (1992) Antibody against the Leu-cam β-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events. Journal of Immunology 148, 1080–1085.Google Scholar
Rothlein, R, Dustin, ML, Marlin, SD and Springer, TA (1986) A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. Journal of Immunology 137, 1270–1274.Google Scholar
Roy, NH, MacKay, JL, Robertson, TF, Hammer, DA and Burkhardt, JK (2018) Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1. Science Signaling 11, eaat3178.Google Scholar
Ruoslahti, E (1988) Fibronectin and its receptors. Annual Review of Biochemistry 57, 375–413.Google Scholar
Ruoslahti, E (1991) Integrins. Journal of Clinical Investigation 87, 1–5.Google Scholar
Ruoslahti, E (1996) RGD and other recognition sequences for integrins. Annual Review of cell and developmental biology 12, 697–715.Google Scholar
Sampath, R, Gallagher, PJ and Pavalko, FM (1998) Cytoskeletal interactions with the leukocyte integrin β2 cytoplasmic tail. Journal of Biological Chemistry 273, 33588–33594.Google Scholar
Sanchez-Madrid, F, Simon, P, Thompson, S and Springer, TA (1983) Mapping of antigenic and functional epitopes on the α- and β-subunits of two related mouse glycoproteins involved in cell interactions. Journal of Experimental Medicine 158, 586–602.Google Scholar
Schneider, H, Valk, E, da Rocha Dias, S, Wei, B and Rudd, CE (2005) CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternative basis for coreceptor function. Proceedings of the National Academy of Sciences of the USA 102, 12861–12866.Google Scholar
Schurpf, T, Chen, Q, Liu, JH, Wang, R, Springer, TA and Wang, JH (2012) The RGD finger of Del-1 is a unique structural feature critical for integrin binding. FASEB Journal 26, 3412–3420.Google Scholar
Schwartz, MA, Schaller, MD and Ginsberg, MH (1995) Integrins: emerging paradigms of signal transduction. Annual Review of Cell and Developmental Biology 11, 549–599.Google Scholar
Scott, LM, Priestley, GV and Papayannopolou, T (2003) Deletion of α4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Molecular and Cellular Biology. doi: 10.1128/MCB.23.24.9349-9360.2003.Google Scholar
Sen, M, Yuki, K and Springer, TA (2013) An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2. Journal of Cell Biology 203, 629–642.Google Scholar
Sen, M, Koksal, AC, Yuki, K, Wang, J and Springer, TA (2018) Ligand- and cation-induced structural alterations of the leukocyte integrin LFA-1. Journal of Biological Chemistry 293, 6565–6577.Google Scholar
Sharma, P and Allison, JP (2015) The future of immune checkpoint therapy. Science 348, 56–61.Google Scholar
Shattil, SJ and Newman, PJ (2004) Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104, 1606–1615.Google Scholar
Shattil, SJ, Cunningham, M and Hoxie, JA (1987) Detection of activated platelets in whole-blood using activation-dependent monoclonal antibodies and flow-cytometry. Blood 70, 307–315.Google Scholar
Shattil, SJ, Kashiwagi, H and Pampori, N (1998) Integrin signaling: the platelet paradigm. Blood 91, 2645–2657.Google Scholar
Shulman, Z, Cohen, SJ, Roediger, B, Kalchenko, V, Jain, RSJ, Grabovsky, V, Klein, E, Shinder, V, Stoler-Barak, L, Feigelson, SW, Nurmi, SM, Goldstein, I, Hartley, O, Gahmberg, CG, Etzioni, A, Weninger, W, Ben-Baruch, A and Alon, R (2012) Transendothelial migration of lymphocytes mediated by endothelial vesicle stores rather than by extracellular chemokine depots. Nature Immunology 13, 67–77.Google Scholar
Sirim, P, Zeitlmann, L, Kellersch, B, Falk, CS, Schendel, DJ and Kolanus, W (2001) Calcium signaling through the β2-cytoplasmic domain of LFA-1 requires intracellular elements of the T cell receptor complex. Journal of Biological Chemistry 276, 42945–42956.Google Scholar
Skinner, JJ, Wang, S, Lee, J, Ong, C, Sommese, R, Sivaramakrishnan, S, Koelmel, W, Hirschbeck, M, Schindelin, H, Kisker, C, Lorenz, K, Sosnick, TR and Rosner, MR (2017) Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome. Proceedings of the National Academy of Sciences of the USA 114, 13453-–13458.Google Scholar
Springer, TA (1990) Adhesion receptors of the immune-system. Nature 346, 425–434.Google Scholar
Springer, TA and Dustin, ML (2012) Integrin inside-out signaling and the immunological synapse. Current Opinion in Cell Biology 24, 107–115.Google Scholar
Springer, TA and Sen, M (2016) Leukocyte integrin αLβ2 headpiece structures: the αI domain, the pocket for the internal ligand, and concerted movements of its loops. Proceedings of the National Academy of Sciences of the USA 113, 2940–2945.Google Scholar
Springer, TA, Thompson, WS, Miller, LJ, Schmalstieg, FC and Anderson, DC (1984) Inherited deficiency of the MAC-1, LFA-1, P150,95 glycoprotein family and its molecular basis. Journal of Experimental Medicine 160, 1901–1918.Google Scholar
Stanley, P, Smith, A, McDowall, A, Nicol, A, Zicha, D and Hogg, N (2008) Intermediate-affinity LFA-1 binds α-actinin-1 to control migration at the leading edge of the T cell. EMBO Journal 27, 62–75.Google Scholar
Stossel, TP, Condeelis, J, Cooley, L, Hartwig, JH, Noegel, A, Schleicher, M and Shapiro, SS (2001) Filamins as integrators of cell mechanics and signalling. Nature Reviews of Molecular Cell Biology 2, 138–145.Google Scholar
Strazza, M, Azoulay-Alfaguter, I, Peled, M, Smrcka, AV, Skolnik, EY, Srivastava, S and Mor, A (2017) PLCε1 regulates SDF-1α-induced lymphocyte adhesion and migration to sites of inflammation. Proceedings of the National Academy of Sciences of the USA 114, 2693–2698.Google Scholar
Stritt, S, Wolf, K, Lorenz, V, Vogtle, T, Gupta, S, Bosl, MR and Nieswandt, B (2015) Rap1-GTP-interacting adaptor molecule (RIAM) is dispensable for platelet integrin activation and function in mice. Blood 125, 219–222.Google Scholar
Strohmeyer, N, Bharadwaj, M, Costell, M, Fässler, R and Muller, DJ (2017) Fibronectin-bound α5β1 integrins sense load and signal to reinforce adhesion in less than a second. Nature Materials 16, 1262–1272.Google Scholar
Su, W, Wynne, J, Pinheiro, EM, Strazza, M, Mor, A, Montenont, E, Berger, J, Paul, DS, Bergmeier, W, Gertler, FB and Philips, MR (2015) Rap1 and its effector RIAM are required for lymphocyte trafficking. Blood 126, 2695–2703.Google Scholar
Sun, Z, Guo, SS and Fässler, R (2016) Integrin-mediated mechanotransduction. Journal of Cell Biology 215, 445–456.Google Scholar
Sun, Z, Costell, M and Fässler, R (2019) Integrin activation by talin, kindlin and mechanical forces. Nature Cell Biology 21, 25–31.Google Scholar
Svensson, L, Howarth, K, McDowall, A, Patzak, I, Evans, R, Ussar, S, Moser, M, Metin, A, Fried, M, Tomlinson, I and Hogg, N (2009) Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nature Medicine 15, 306–312.Google Scholar
Tadokoro, S, Shattil, SJ, Eto, K, Tai, V, Liddington, RC, de Pereda, JM, Ginsberg, MH and Calderwood, DA (2003) Talin binding to integrin β tails: a final common step in integrin activation. Science 302, 103–106.Google Scholar
Takada, Y, Ye, X and Simon, S (2007) The integrins. Genome Biology 8, 215.Google Scholar
Takafuta, T, Sacki, M, Fujimoto, TT, Fujimura, K and Shapiro, SS (2003) A new member of the LIM protein family binds to filamin B and localizes at stress fibers. Journal of Biological Chemistry 278, 12175–12181.Google Scholar
Takahashi, M, Dillon, TJ, Liu, C, Kariya, Y, Wang, Z and Stork, PJS (2013) PKA-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration. Journal of Biological Chemistry 216, 27712–27723.Google Scholar
Takala, H, Nurminen, E, Nurmi, SM, Aatonen, M, Strandin, T, Takatalo, M, Kiema, T, Gahmberg, CG, Ylänne, J and Fagerholm, SC (2008) Β2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding. Blood 112, 1853–1862.Google Scholar
Takeichi, M (1977) Functional correlation between cell adhesion properties and some cell-surface proteins. Journal of Cell Biology 75, 464–474.Google Scholar
Takeichi, M (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451–1455.Google Scholar
Tan, S-M, Robinson, MK, Drbal, K, van Kooyk, Y, Shaw, JM and Law, SKA (2001) The N-terminal region and the mid-region complex of the integrin β2 subunit. Journal of Biological Chemistry 276, 36370–36376.Google Scholar
Thomas, ML (1989) The leukocyte common antigen family. Annual Review of Immunology 7, 339–369.Google Scholar
Tian, L, Yoshihara, Y, Mizuno, T, Mori, K and Gahmberg, CG (1997) The neuronal glycoprotein, telencephalin, is a cellular ligand for the CD11a/CD18 leukocyte integrin. Journal of Immunology 158, 928–936.Google Scholar
Tian, L, Lappalainen, J, Autero, M, Hänninen, S, Rauvala, H and Gahmberg, CG (2008) Shedded neuronal ICAM-5 suppresses T cell activation. Blood 111, 3615–3625.Google Scholar
Tirupula, KC, Ithychanda, SS, Mohan, ML, Prasad, SVN, Qin, J and Karnik, SS (2015) G protein-coupled receptors directly bind filamin A with high affinity and promote filamin phosphorylation. Biochemistry 54, 6673–6683.Google Scholar
Tng, E, Tan, S-M, Ranganathan, S, Cheng, M and Law, SKA (2004) The integrin αLβ2 hybrid domain serves as a link for the propagation of activation signal from its stalk regions to the I-like domain. Journal of Biological Chemistry 279, 54334–54339.Google Scholar
Tohyama, Y, Katagiri, K, Pardi, R, Lu, C, Springer, TA and Kinashi, T (2003) The critical cytoplasmic regions of the αL/β2 integrin in Rap1-induced adhesion and migration. Molecular Biology of the Cell 14, 2570–2582.Google Scholar
Trowbridge, IS (1978) Interspecies spleen-myeloma hybrid producing monoclonal antibodies against mouse lymphocyte surface glycoprotein, T200. Journal of Experimental Medicine 148, 313–323.Google Scholar
Tseng, H-Y, Samarelli, AV, Kammerer, P, Scholze, S, Ziegler, T, Immier, R, Zent, R, Sperandio, M, Sanders, CR, Fässler, R and Böttcher, RT (2018) LCP1 preferentially binds clasped αMβ2 integrin and attenuates leukocyte adhesion under flow. Journal of Cell Science 131. doi: 10.1242/jcs.218214.Google Scholar
Tu, Y, Wu, S, Shi, X, Chen, K and Wu, C (2003) Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell 113, 37–47.Google Scholar
Uotila, LM, Aatonen, M and Gahmberg, CG (2013) Integrin CD11c/CD18 α-chain phosphorylation is functionally important. Journal of Biological Chemistry 288, 33494–33499.Google Scholar
Uotila, LM, Jahan, F, Hinojosa, LS, Melandri, E, Grönholm, M and Gahmberg, CG (2014) Specific phosphorylations transmit signals from leukocyte β2 to β1 integrins and regulate adhesion. Journal of Biological Chemistry 289, 32230–32242.Google Scholar
Ussar, S, Wang, HV, Linder, S, Fässler, R and Moser, M (2006) The Kindlins: subcellular localization and expression during murine development. Experimental Cell Research 312, 3142–3151.Google Scholar
Valmu, L and Gahmberg, CG (1995) Treatment with okadaic acid reveals strong threonine phosphorylation of CD18 after activation of CD11/CD18 leukocyte integrin with phorbol esters or CD3 antibodies. Journal of Immunology 155, 1175–1183.Google Scholar
Valmu, L, Autero, M, Siljander, P, Patarroyo, M and Gahmberg, CG (1991) Phosphorylation of the β-subunit of CD11/CD18 integrins by protein kinase C correlates with leukocyte adhesion. European Journal of Immunology 21, 2857–2862.Google Scholar
Valmu, L, Fagerholm, S, Suila, H and Gahmberg, CG (1999) The cytoskeletal association of CD11/CD18 leukocyte integrins in phorbol ester activated T cells correlates with CD18 phosphorylation. European Journal of Immunology 29, 2107–2118.Google Scholar
Vestweber, D (2015) How leukocytes cross the vascular endothelium. Nature Reviews of Immunology 15, 692–704.Google Scholar
Vinogradova, O, Velyvis, A, Velyviene, A, Hu, B, Haas, TA, Plow, EF and Qin, J (2002) A structural mechanism of integrin αIIbβ3 ‘inside-out’ activation as regulated by its cytoplasmic face. Cell 110, 587–597.Google Scholar
Waldt, N, Seifert, A, Demiray, YE, Devroe, E, Turk, BE, Reichardt, P, Mix, C, Reinhold, A, Freund, C, Muller, AJ, Schraven, B, Stork, O and Kliche, S (2018) Filamin phosphorylation at serine 2152 by the serine/threonine kinase Ndr2 controls TCR-induced LFA-1 activation in T cells. Frontiers in Immunology 9, Article 2852. doi: 10.3389/fimmu.2018.02852.Google Scholar
Walz, G, Aruffo, A, Kolanus, W, Bevilacqua, M and Seed, B (1990) Recognition by ELAM-1 of the sialyl-LeX determinant on myeloid and tumor cells. Science 250, 1132–1135.Google Scholar
Wei, X, Wang, X, Zhan, J, Chen, Y, Fang, W, Zhang, L and Zhang, H (2017) Smurf1 inhibits integrin activation by controlling kindlin-2 ubiquitination and degradation. Journal of Cell Biology 216, 1455–1471.Google Scholar
Weitz-Schmidt, G, Welzenbach, K, Brinkmann, V, Kamata, T, Kallen, J, Bruns, C, Cottens, S, Takada, Y and Hommel, U (2001) Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nature Medicine 7, 687–692.Google Scholar
Wickham, TJ, Mathias, P, Cheresh, DA and Nemerow, GR (1993) Integrins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment. Cell 73, 309–319.Google Scholar
Wonerow, P, Pearce, AC, Vaux, DJ and Watson, SP (2003) A critical role for phospholipase C gamma2 in alphaIIbbeta3-mediated platelet spreading. Journal of Biological Chemistry 278, 37520–37529.Google Scholar
Wu, Y, Span, LM, Nygren, P, Zhu, H, Moore, DT, Cheng, H, Roder, H, DeGrado, WF and Bennett, JS (2015) The tyrosine kinase c-Src specifically binds to the active integrin αIIbβ3 to initiate outside-in signaling in platelets. Journal of Biological Chemistry 290, 15825–15834.Google Scholar
Xie, C, Zhu, J, Chen, X, Mi, L, Nishida, N and Springer, TA (2010) Structure of an integrin with an αI domain, complement receptor type 4. EMBO Journal 29, 666–679.Google Scholar
Xiong, J-P, Stehle, T, Diefenbach, B, Zhang, R, Dunker, R, Scott, DI, Joachimiak, A, Goodman, SL and Arnaout, MA (2001) Crystal structure of the extracellular segment of integrin αVβ3. Science 294, 339–345.Google Scholar
Xiong, J-P, Mahalingham, B, Alonso, JL, Borrelli, LA, Rui, X, Anand, S, Hyman, TR, Rysiok, T, Muller-Pompalla, D, Goodman, SL and Arnaout, MA (2009) Crystal structure of the complete integrin αVβ3 ectodomain plus an α/β transmembrane fragment. Journal of Cell Biology 186, 589–600.Google Scholar
Yamada, KM (1983) Cell surface interactions with extracellular materials. Annual Review of Biochemistry 52, 761–799.Google Scholar
Yamada, KM and Olden, K (1978) Fibronectins – adhesive glycoproteins of cell – surface and blood. Nature 275, 179–184.Google Scholar
Ye, F, Petrich, BG, Anekal, P, Lefort, CT, Kasirer-Friede, A, Shattil, SJ, Ruppert, R, Moser, M, Fässler, R and Ginsberg, MH (2013 a) The mechanism of kindlin-mediated activation of integrin αIIbβ3. Current Biology 23, 2288–2295.Google Scholar
Ye, Q, Feng, Y, Yin, Y, Faucher, F, Currie, MA, Rahman, MN, Jin, J, Li, S, Wei, Q and Jia, Z (2013 b) Structural basis of calcineurin activation by calmodulin. Cell Signaling 25, 2661–2667.Google Scholar
Ylänne, J, Huuskonen, J, O'Toole, TE, Ginsberg, MH, Virtanen, I and Gahmberg, CG (1995) Mutation of the cytoplasmic domain of the integrin β3 subunit: differential effects on cell spreading, recruitment to adhesion plaques, endocytosis and phagocytosis. Journal of Biological Chemistry 270, 9550–9557.Google Scholar
Yoshihara, Y, Oka, S, Nemoto, Y, Watanabe, Y, Nagata, S, Kagamiyama, H and Mori, K (1994) An ICAM-related neuron glycoprotein, telencephalin, with brain segment-specific expression. Neuron 12, 541–553.Google Scholar
Zaidel-Bar, R, itzkovitz, S, Ma àyan, A, Iyengar, R and Geiger, B (2007) Functional atlas of the integrin adhesome. Nature Cell Biology 9, 858–868.Google Scholar
Zarbock, A, Ley, K, McEver, RP and Hidalgo, A (2011) Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118, 6743–6751.Google Scholar
Zeltz, C and Gullberg, D (2016) The integrin - collagen connection - a glue for tissue repair? Journal of Cell Science 129, 653–664.Google Scholar
Zhou, Z-R, Gao, H-C, Zhou, C-J, Chang, Y-G, Hong, J, Song, A-X, Lin, D-H and Hu, H-Y (2008) Differential ubiquitin binding of the UBA domains from human c-Cbl and Cbl-b: NMR structural and biochemical insights. Protein Science 17, 1805–1814.Google Scholar
Zhu, L, Yang, J, Bromberger, T, Holly, A, Lu, F, Liu, H, Sun, K, Klapproth, S, Hirbawi, J, Byzova, TV, Plow, EF, Moser, M and Qin, J (2017) Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nature Communications 8, 1744.Google Scholar