Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-30T23:39:13.023Z Has data issue: false hasContentIssue false

8 - Reporter Gene Imaging of Cell Signal Transduction

Published online by Cambridge University Press:  07 September 2010

Sanjiv Sam Gambhir
Affiliation:
Stanford University School of Medicine, California
Shahriar S. Yaghoubi
Affiliation:
Stanford University School of Medicine, California
Get access

Summary

INTRODUCTION

Signal transduction pathways enable cells to act in response to the perception of stimuli in their environment and the integration of external and internal signals by changes in transcriptional activity, metabolism, or other regulatory measures. The proper functioning of these pathways is vital for cell adaptation and survival under varying conditions, as well as for cell differentiation, fate, and death.

Cell signal transduction can be simplistically recognized as three steps: reception, transduction, and induction. Reception entails the binding of a signal molecule (e.g., a hormone) to its specific receptor. Transduction is the process by which, for example, a second messenger is formed in or released into the cytosol, thus amplifying the stimulus and initiating the cell's response to the signal. Induction results in activation of the cellular process.

The study of individual cells and cell lines allows us to identify features of signal transduction, but work on physiological models defines what is relevant in the physiology of a given cell type at a given stage. Indeed, the simplified experimental paradigms of conventional cell biology systems used for the study of signal transduction are a double-edged sword. At each level from the in vivo microscopic study of protein–protein interactions (PPIs) in single cells to the precise molecular structural definition of proteins by X-ray crystallography, what we gain in precision, rigor, and definition we may lose in relevant biology.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2010

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

Klipp, E., Liebermeister, W. (2006). Mathematical modeling of intracellular signaling pathways. BMC Neurosci 7 (Suppl 1): S10.CrossRefGoogle ScholarPubMed
Dumont, J. E., Dremier, S., Pirson, I., Maenhaut, C. (2002). Cross signaling, cell specificity, and physiology. Am J Physiol Cell Physiol 283: C2–28.CrossRefGoogle ScholarPubMed
Massoud, T. F., Gambhir, S. S. (2003). Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17: 545–580.CrossRefGoogle Scholar
Livingston, J. N. (1999). Genetically engineered mice in drug development. J Intern Med 245: 627–635.CrossRefGoogle ScholarPubMed
Gassmann, M., Hennet, T. (1998). From genetically altered mice to integrative physiology. News Physiol Sci 13: 53–57.Google ScholarPubMed
Gambhir, S. S., Barrio, J. R., Herschman, H. R., Phelps, M. E. (1999). Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol 26: 481–490.CrossRefGoogle ScholarPubMed
Massoud, T. F., Singh, A., Gambhir, S. S. (2008). Noninvasive molecular neuroimaging using reporter genes: part II, experimental, current, and future applications. AJNR Am J Neuroradiol 29: 409–418.CrossRefGoogle ScholarPubMed
Burns, M. E., Arshavsky, V. Y. (2005). Beyond counting photons: trials and trends in vertebrate visual transduction. Neuron 48: 387–401.CrossRefGoogle ScholarPubMed
Ronnett, G. V., Moon, C. G. (2002). Proteins and olfactory signal transduction. Annu Rev Physiol 64: 189–222.CrossRefGoogle ScholarPubMed
Wong, G. T., Gannon, K. S., Margolskee, R. F. (1996). Transduction of bitter and sweet taste by gustducin. Nature 381: 796–800.CrossRefGoogle ScholarPubMed
Singh, A. B., Harris, R. C. (2005). Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal 17: 1183–1193.CrossRefGoogle ScholarPubMed
Gnecchi, M., Zhang, Z., Ni, A., Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103: 1204–1219.CrossRefGoogle ScholarPubMed
Weijer, C. J. (2003). Visualizing signals moving in cells. Science 300: 96–100.CrossRefGoogle ScholarPubMed
Levitzki, A. (2004). Introduction: signal transduction therapy-10 years later. Semin Cancer Biol 14: 219–221.CrossRefGoogle ScholarPubMed
Koman, A., Harayama, S., Hazelbauer, G. L. (1979). Relation of chemotactic response to the amount of receptor: evidence for different efficiencies of signal transduction. J Bacteriol 138: 739–747.Google ScholarPubMed
Heldin, C. H. (2001). Signal transduction: multiple pathways, multiple options for therapy. Stem Cells 19: 295–303.CrossRefGoogle ScholarPubMed
Nahta, R., Yu, D., Hung, M. C., Hortobagyi, G. N., Esteva, F. J. (2006). Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 3: 269–280.CrossRefGoogle ScholarPubMed
Malmberg, N. J., Falke, J. J. (2005). Use of EPR power saturation to analyze the membrane-docking geometries of peripheral proteins: applications to C2 domains. Annu Rev Biophys Biomol Struct 34: 71–90.CrossRefGoogle ScholarPubMed
Hanson, M. A., Stevens, R. C. (2009). Discovery of new GPCR biology: one receptor structure at a time. Structure 17: 8–14.CrossRefGoogle ScholarPubMed
Lefkowitz, R. J. (2004). Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol Sci 25: 413–422.CrossRefGoogle ScholarPubMed
Collingridge, G. L., Olsen, R., Peters, J. A., Spedding, M. (2009). Ligand gated ion channels. Neuropharmacology 56: 1.CrossRefGoogle ScholarPubMed
Pless, S. A., Lynch, J. W. (2008). Illuminating the structure and function of Cys-loop receptors. Clin Exp Pharmacol Physiol 35: 1137–1142.CrossRefGoogle ScholarPubMed
Swanson, G. T., Sakai, R. (2009). Ligands for ionotropic glutamate receptors. Prog Mol Subcell Biol 46: 123–157.CrossRefGoogle ScholarPubMed
Jarvis, M. F., Khakh, B. S. (2009). ATP-gated P2X cation-channels. Neuropharmacology 56: 208–215.CrossRefGoogle ScholarPubMed
Kucharova, S., Farkas, R. (2002). Hormone nuclear receptors and their ligands: role in programmed cell death (review). Endocr Regul 36: 37–60.Google Scholar
Chalmers, M., Schell, M. J., Thorn, P. (2006). Agonist-evoked inositol trisphosphate receptor (IP3R) clustering is not dependent on changes in the structure of the endoplasmic reticulum. Biochem J 394 (Pt 1): 57–66.CrossRefGoogle Scholar
Hardingham, G. E., Bading, H. (1999). Calcium as a versatile second messenger in the control of gene expression. Microsc Res Tech 46: 348–355.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Takai, N., Ueda, T., Nasu, K., Yamashita, S., Toyofuku, M., Narahara, H. (2009). Targeting calcium/calmodulin-dependence kinase I and II as a potential anti-proliferation remedy for endometrial carcinomas. Cancer Lett 277: 235–243.CrossRefGoogle ScholarPubMed
Tu, P., Kunert-Keil, C., Lucke, S., Brinkmeier, H., Bouron, A. (2009). Diacylglycerol analogues activate second messenger-operated calcium channels exhibiting TRPC-like properties in cortical neurons. J Neurochem 108: 126–138.CrossRefGoogle ScholarPubMed
Kalinowski, L., Dobrucki, L. W., Malinski, T. (2001). Nitric oxide as a second messenger in parathyroid hormone-related protein signaling. J Endocrinol 170: 433–440.CrossRefGoogle ScholarPubMed
Normanno, N., Luca, A., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., Feo, G., Caponigro, F., Salomon, D. S. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366: 2–16.CrossRefGoogle Scholar
Wang, Z., Li, Y., Banerjee, S., Sarkar, F. H. (2008). Exploitation of the Notch signaling pathway as a novel target for cancer therapy. Anticancer Res 28: 3621–3630.Google ScholarPubMed
McEwan, I. J. (2009). Nuclear receptors: one big family. Methods Mol Biol 505: 3–18.CrossRefGoogle ScholarPubMed
Lo, H. W., Hsu, S. C., Hung, M. C. (2006). EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Res Treat 95: 211–218.CrossRefGoogle ScholarPubMed
Downward, J. (2003). Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3: 11–22.CrossRefGoogle ScholarPubMed
LoPiccolo, J., Blumenthal, G. M., Bernstein, W. B., Dennis, P. A. (2008). Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11: 32–50.CrossRefGoogle ScholarPubMed
Kfir, S., Ehrlich, M., Goldshmid, A., Liu, X., Kloog, Y., Henis, Y. I. (2005). Pathway- and expression level-dependent effects of oncogenic N-Ras: p27(Kip1) mislocalization by the Ral-GEF pathway and Erk-mediated interference with Smad signalling. Mol Cell Biol 25: 8239–8250.CrossRefGoogle Scholar
Li, W. X. (2008). Canonical and non-canonical JAK-STAT signalling. Trends Cell Biol 18: 545–551.CrossRefGoogle Scholar
Harburger, D. S., Calderwood, D. A. (2009). Integrin signalling at a glance. J Cell Sci 122: 159–163.CrossRefGoogle ScholarPubMed
Takigawa, Y., Brown, A. M. (2008). Wnt signaling in liver cancer. Curr Drug Targets 9: 1013–1024.CrossRefGoogle ScholarPubMed
Bhola, N. E., Grandis, J. R. (2008). Crosstalk between G-protein-coupled receptors and epidermal growth factor receptor in cancer. Front Biosci 13: 1857–1865.CrossRefGoogle Scholar
Baud, V., Karin, M. (2009). Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8: 33–40.CrossRefGoogle ScholarPubMed
Tian, M., Schiemann, W. P. (2009). The TGF-beta paradox in human cancer: an update. Future Oncol 5: 259–271.CrossRefGoogle ScholarPubMed
Jiang, J., Hui, C. C. (2008). Hedgehog signaling in development and cancer. Dev Cell 15: 801–812.CrossRefGoogle ScholarPubMed
Smith, N. J., Luttrell, L. M. (2006). Signal switching, crosstalk, and arrestin scaffolds: novel G protein-coupled receptor signaling in cardiovascular disease. Hypertension 48: 173–179.CrossRefGoogle Scholar
Schwartz, M. A., Baron, V. (1999). Interactions between mitogenic stimuli, or, a thousand and one connections. Curr Opin Cell Biol 11: 197–202.CrossRefGoogle ScholarPubMed
O'Neill, L. A. (2008). When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunity 29: 12–20.CrossRefGoogle ScholarPubMed
Chen, M., Lin, S., Hofestaedt, R. (2004). STCDB: Signal Transduction Classification Database. Nucleic Acids Res 32: D456–458.CrossRefGoogle ScholarPubMed
Weng, G., Bhalla, U. S., Iyengar, R. (1999). Complexity in biological signaling systems. Science 284: 92–96.CrossRefGoogle ScholarPubMed
Hood, L., Heath, J. R., Phelps, M. E., Lin, B. (2004). Systems biology and new technologies enable predictive and preventative medicine. Science 306: 640–643.CrossRefGoogle ScholarPubMed
Royer, C. (2004). Protein-protein interactions. Available from: http://www.biophysics.org/education/croyer.pdf
Engen, J. R., Wales, T. E., Hochrein, J. M., Meyn, M. A. 3rd, Banu Ozkan, S., Bahar, I., Smithgall, T. E. (2008). Structure and dynamic regulation of Src-family kinases. Cell Mol Life Sci 65: 3058–3073.CrossRefGoogle ScholarPubMed
Uhlik, M. T., Temple, B., Bencharit, S., Kimple, A. J., Siderovski, D. P., Johnson, G. L. (2005). Structural and evolutionary division of phosphotyrosine binding (PTB) domains. J Mol Biol 345: 1–20.CrossRefGoogle ScholarPubMed
Jemth, P., Gianni, S. (2007). PDZ domains: folding and binding. Biochemistry 46: 8701–8708.CrossRefGoogle Scholar
Grunewald, T. G., Butt, E. (2008). The LIM and SH3 domain protein family: structural proteins or signal transducers or both?Mol Cancer 7: 31.CrossRefGoogle ScholarPubMed
Lemmon, M. A. (2007). Pleckstrin homology (PH) domains and phosphoinositides. Biochem Soc Symp 74: 81–93.CrossRefGoogle Scholar
Ilsley, J. L., Sudol, M., Winder, S. J. (2002). The WW domain: linking cell signalling to the membrane cytoskeleton. Cell Signal 14: 183–189.CrossRefGoogle ScholarPubMed
Weidemann, T., Höfinger, S., Müller, K., Auer, M. (2007). Beyond dimerization: a membrane-dependent activation model for interleukin-4 receptor-mediated signaling. J Mol Biol 366: 1365–1373.CrossRefGoogle Scholar
Smith, T. F. (2008). Diversity of WD-repeat proteins. Subcell Biochem 48: 20–30.CrossRefGoogle ScholarPubMed
Yamada, K., Miyamoto, K. (2005). Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli. Front Biosci 10: 3151–3171.CrossRefGoogle ScholarPubMed
Manna, P. R., Dyson, M. T., Stocco, D. M. (2009). Role of basic leucine zipper proteins in transcriptional regulation of the steroidogenic acute regulatory protein gene. Mol Cell Endocrinol 302: 1–11.CrossRefGoogle ScholarPubMed
Zhang, J., Allen, M. D. (2007). FRET-based biosensors for protein kinases: illuminating the kinome. Mol Biosyst 3: 759–765.CrossRefGoogle ScholarPubMed
Massoud, T. F., Paulmurugan, R., Gambhir, S. S. (2004). Molecular imaging of homodimeric protein-protein interactions in living subjects. FASEB J 18: 1105–1107.CrossRefGoogle ScholarPubMed
Wehrman, T., Kleaveland, B., Her, J. H., Balint, R. F., Blau, H. M. (2002). Protein-protein interactions monitored in mammalian cells via complementation of beta-lactamase enzyme fragments. Proc Natl Acad Sci USA 99: 3469–3474.CrossRefGoogle ScholarPubMed
Truong, K., Ikura, M. (2001). The use of FRET imaging microscopy to detect protein-protein interactions and protein conformational changes in vivo. Curr Opin Struct Biol 11: 573–578.CrossRefGoogle ScholarPubMed
Hu, C. D., Chinenov, Y., Kerppola, T. K. (2002). Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell 9: 789–798.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Gambhir, S. S. (2003). Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation. Anal Chem 75: 1584–1589.CrossRefGoogle ScholarPubMed
Rudin, M. (2008). Noninvasive imaging of receptor function: signal transduction pathways and physiological readouts. Curr Opin Drug Discov Devel 11: 606–615.Google ScholarPubMed
Doubrovin, M., Ponomarev, V., Beresten, T., Balatoni, J., Bornmann, W., Finn, R., Humm, J., Larson, S., Sadelain, M., Blasberg, R., Gelovani Tjuvajev, J. (2001). Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA 98: 9300–9305.CrossRefGoogle ScholarPubMed
Wiele, C., Boersma, H., Dierckx, R. A., Spiegeleer, B., Waarde, A., Elsinga, P. H. (2008). Growth factor/peptide receptor imaging for the development of targeted therapy in oncology. Curr Pharm Des 14: 3340–3347.CrossRefGoogle Scholar
Elsässer-Beile, U., Reischl, G., Wiehr, S., Bühler, P., Wolf, P., Alt, K., Shively, J., Judenhofer, M. S., Machulla, H. J., Pichler, B. J. (2009). PET imaging of prostate cancer xenografts with a highly specific antibody against the prostate-specific membrane antigen. J Nucl Med 50: 606–611.CrossRefGoogle ScholarPubMed
Macfarlane, D., Socrates, A., Eisenberg, P., Larcos, G., Roach, P., Gerometta, M., Smart, R., Tsui, W., Scott, A. M. (2009). Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab' fragment (99mTc-DI-DD3B6/22–80B3): results of a phase I trial. Eur J Nucl Med Mol Imaging 36: 250–259.CrossRefGoogle ScholarPubMed
Leyton, J. V., Olafsen, T., Lepin, E. J., Hahm, S., Bauer, K. B., Reiter, R. E., Wu, A. M. (2008). Humanized radioiodinated minibody for imaging of prostate stem cell antigen-expressing tumors. Clin Cancer Res 14: 7488–7496.CrossRefGoogle ScholarPubMed
Zaccaro, L., Del Gatto, A., Pedone, C., Saviano, M. (2009). Peptides for tumour therapy and diagnosis: current status and future directions. Curr Med Chem 16: 780–795.CrossRefGoogle ScholarPubMed
Bose, S. K., Turkheimer, F. E., Howes, O. D., Mehta, M. A., Cunliffe, R., Stokes, P. R., Grasby, P. M. (2008). Classification of schizophrenic patients and healthy controls using [18F] fluorodopa PET imaging. Schizophr Res 106: 148–155.CrossRefGoogle Scholar
Marek, K., Jennings, D. (2009). Can we image premotor Parkinson disease?Neurology 72: S21–26.CrossRefGoogle ScholarPubMed
Wagner, H. N., Dannals, R. F., Frost, J. J., Wong, D. F., Ravert, H. T., Wilson, A. A., Links, J. M., Burns, H. D., Kuhar, M. J., Snyder, S. H. (1985). Imaging neuroreceptors in the human brain in health and disease. Radioisotopes 34:103–107.CrossRefGoogle ScholarPubMed
Wong, D. F., Singer, H. S., Brandt, J., Shaya, E., Chen, C., Brown, J., Kimball, A. W., Gjedde, A., Dannals, R. F., Ravert, H. T., Wilson, P. D., Wagner, H. N. (1997). D2-like dopamine receptor density in Tourette syndrome measured by PET. J Nucl Med 38: 1243–1247.Google ScholarPubMed
Vlaar, A. M., Nijs, T., Kessels, A. G., Vreeling, F. W., Winogrodzka, A., Mess, W. H., Tromp, S. C., Kroonenburgh, M. J., Weber, W. E. (2008). Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. Eur Neurol 59: 258–266.CrossRefGoogle ScholarPubMed
Nikolaus, S., Antke, C., Kley, K., Poeppel, T. D., Hautzel, H., Schmidt, D., Müller, H. W. (2007a). Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans. Rev Neurosci 18: 439–472.Google ScholarPubMed
Nikolaus, S., Larisch, R., Beu, M., Antke, C., Kley, K., Forutan, F., Wirrwar, A., Müller, H. W. (2007b). Investigating the dopaminergic synapse in vivo. II. Molecular imaging studies in small laboratory animals. Rev Neurosci 18: 473–504.Google ScholarPubMed
Costes, N., Merlet, I., Ostrowsky, K., Faillenot, I., Lavenne, F., Zimmer, L., Ryvlin, P., Bars, D. (2005). A 18F-MPPF PET normative database of 5-HT1A receptor binding in men and women over aging. J Nucl Med 46: 1980–1989.Google ScholarPubMed
Hirano, S., Shinotoh, H., Arai, K., Aotsuka, A., Yasuno, F., Tanaka, N., Ota, T., Sato, K., Fukushi, K., Tanada, S., Hattori, T., Irie, T. (2008). PET study of brain acetylcholinesterase in cerebellar degenerative disorders. Mov Disord 23: 1154–1160.CrossRefGoogle ScholarPubMed
Sihver, W., Fasth, K. J., Ogren, M., Lundqvist, H., Bergström, M., Watanabe, Y., Långström, B., Nordberg, A. (1999). In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in rhesus monkeys. Nucl Med Biol 26: 633–640.CrossRefGoogle ScholarPubMed
Oosten, E. M., Wilson, A. A., Stephenson, K. A., Mamo, D. C., Pollock, B. G., Mulsant, B. H., Yudin, A. K., Houle, S., Vasdev, N. (2009). An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP. Appl Radiat Isot 67: 611–616.CrossRefGoogle Scholar
Newberg, A. B., Ray, R., Scheuermann, J., Wintering, N., Saffer, J., Schmitz, A., Freifelder, R., Karp, J., Lerman, C., Divgi, C. (2009). Dosimetry of 11C-carfentanil, a mu-opioid receptor imaging agent. Nucl Med Commun 30: 314–318.CrossRefGoogle Scholar
Weerts, E. M., Kim, Y. K., Wand, G. S., Dannals, R. F., Lee, J. S., Frost, J. J., McCaul, M. E. (2008). Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacology 33: 653–665.CrossRefGoogle ScholarPubMed
Kim, S. E., Szabo, Z., Seki, C., Ravert, H. T., Scheffel, U., Dannals, R. F., Wagner, H. N. (1999). Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors. Ann Nucl Med 13: 101–107.CrossRefGoogle Scholar
Johansson, A., Engler, H., Blomquist, G., Scott, B., Wall, A., Aquilonius, S. M., Långström, B., Askmark, H. (2007). Evidence for astrocytosis in ALS demonstrated by [11C](L)-deprenyl-D2 PET. J Neurol Sci 255: 17–22.CrossRefGoogle Scholar
Reubi, J. C., Maecke, H. R. (2008). Peptide-based probes for cancer imaging. J Nucl Med 49: 1735–1738.CrossRefGoogle ScholarPubMed
Moody, T. W., Gozes, I. (2007). Vasoactive intestinal peptide receptors: a molecular target in breast and lung cancer. Curr Pharm Des 13: 1099–1104.CrossRefGoogle ScholarPubMed
Degenfeld, G., Wehrman, T. S., Hammer, M. M., Blau, H. M. (2007). A universal technology for monitoring G-protein-coupled receptor activation in vitro and noninvasively in live animals. FASEB J 21: 3819–3826.CrossRefGoogle Scholar
Rossi, F., Charlton, C. A., Blau, H. M. (1997). Monitoring protein-protein interactions in intact eukaryotic cells by beta-galactosidase complementation. Proc Natl Acad Sci USA 94: 8405–8410.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Gambhir, S. S. (2006). An intramolecular folding sensor for imaging estrogen receptor-ligand interactions. Proc Natl Acad Sci USA 103: 15883–15888.CrossRefGoogle ScholarPubMed
Förster, T. (1948). Intermolecular energy transference and fluorescence. Ann Phys 2: 54–75.Google Scholar
De, A., Gambhir, S. S. (2005). Noninvasive imaging of protein-protein interactions from live cells and living subjects using bioluminescence resonance energy transfer. FASEB J 19: 2017–2019.CrossRefGoogle ScholarPubMed
De, A., Loening, A. M., Gambhir, S. S. (2007). An improved bioluminescence resonance energy transfer strategy for imaging intracellular events in single cells and living subjects. Cancer Res 67: 7175–7183.CrossRefGoogle ScholarPubMed
Levi, J., De, A., Cheng, Z., Gambhir, S. S. (2007). Bisdeoxycoelenterazine derivatives for improvement of bioluminescence resonance energy transfer assays. J Am Chem Soc 129: 11900–11901.CrossRefGoogle ScholarPubMed
De, A., Ray, P., Loening, A. M., Gambhir, S. S. (2009). BRET3: A red-shifted bioluminescence resonance energy transfer (BRET) based integrated platform for imaging protein-protein interactions from single live cell and living animals. FASEB J 23: 2702-2709.CrossRefGoogle ScholarPubMed
Chan, C. T., Paulmurugan, R., Reeves, R. E., Solow-Cordero, D., Gambhir, S. S. (2008). Molecular imaging of phosphorylation events for drug development. Mol Imaging Biol 11: 144-158.CrossRefGoogle ScholarPubMed
Zhang, L., Lee, K. C., Bhojani, M. S., Khan, A. P., Shilman, A., Holland, E. C., Ross, B. D., Rehemtulla, A. (2007). Molecular imaging of Akt kinase activity. Nat Med 13: 1114–1119.CrossRefGoogle ScholarPubMed
Zhang, L., Bhojani, M. S., Ross, B. D., Rehemtulla, A. (2008). Enhancing Akt imaging through targeted reporter expression. Mol Imaging 7: 168–174.CrossRefGoogle ScholarPubMed
Xu, C. W., Mendelsohn, A. R., Brent, R. (1997). Cells that register logical relationships among proteins. Proc Natl Acad Sci USA 94: 12473–12478.CrossRefGoogle ScholarPubMed
Pelletier, J. N., Campbell-Valois, F., Michnick, S. W. (1998). Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments. Proc Natl Acad Sci USA 95: 12141–12146.CrossRefGoogle ScholarPubMed
Johnsson, N., Varshavsky, A. (1994). Split ubiquitin as a sensor of protein interactions in vivo. Proc Natl Acad Sci USA 91: 10340–10344.CrossRefGoogle ScholarPubMed
Michnick, S. W., Remy, I., Campbell-Valois, F. X., Vallee-Balisle, A., Pelletier, J. N. (2000). Detection of protein-protein interactions by protein fragment complementation strategies. Methods Enzymol 328: 208–230.CrossRefGoogle ScholarPubMed
Hu, C. D., Kerppola, T. K. (2003). Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis. Nat Biotech 21: 539–545.CrossRefGoogle ScholarPubMed
Galarneau, A., Primeau, M., Trudeau, L. E., Michnick, S. W. (2002). Beta-lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein-protein interactions. Nat Biotechnol 20: 619–622.CrossRefGoogle ScholarPubMed
Spotts, J. M., Dolmetsch, R. E., Greenberg, M. E. (2002). Time-lapse imaging of a dynamic phosphorylation-dependent protein-protein interaction in mammalian cells. Proc Natl Acad Sci USA 99: 15142–15147.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Umezawa, Y., Gambhir, S. S. (2002). Noninvasive imaging of protein-protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proc Natl Acad Sci USA 99: 15608–15613.CrossRefGoogle ScholarPubMed
Kaihara, A., Kawai, Y., Sato, M., Ozawa, T., Umezawa, Y. (2003). Locating a protein-protein interaction in living cells via split Renilla luciferase complementation. Anal Chem 75: 4176–4181.CrossRefGoogle ScholarPubMed
Ozawa, T., Umezawa, Y. (2001). Detection of protein-protein interactions in vivo based on protein splicing. Curr Opin Chem Biol 5: 578–583.CrossRefGoogle ScholarPubMed
Luker, K. E., Smith, M. C., Luker, G. D., Gammon, S. T., Piwnica-Worms, H., Piwnica-Worms, D. (2004). Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proc Natl Acad Sci USA 101: 12288–12293.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Gambhir, S. S. (2007). Combinatorial library screening for developing an improved split-firefly luciferase fragment-assisted complementation system for studying protein-protein interactions. Anal Chem 79: 2346–2353.CrossRefGoogle ScholarPubMed
Choi, C. Y., Chan, D. A., Paulmurugan, R., Sutphin, P. D., Le, Q. T., Koong, A. C., Zundel, W., Gambhir, S. S., Giaccia, A. J. (2008). Molecular imaging of hypoxia-inducible factor 1 alpha and von Hippel-Lindau interaction in mice. Mol Imaging 7: 139–146.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Gambhir, S. S. (2003). Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation. Anal Chem 75: 1584–1589.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Massoud, T. F., Huang, J., Gambhir, S. S. (2004). Molecular imaging of drug-modulated protein-protein interactions in living subjects. Cancer Res 64: 2113–2119.CrossRefGoogle ScholarPubMed
Bhaumik, S., Gambhir, S. S. (2002). Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci USA 99: 377–382.CrossRefGoogle ScholarPubMed
Paulmurugan, R., Gambhir, S. S. (2005). Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals. Cancer Res 65: 7413–7420.CrossRefGoogle ScholarPubMed
Kim, S. B., Ozawa, T., Watanabe, S., Umezawa, Y. (2004). High-throughput sensing and noninvasive imaging of protein nuclear transport by using reconstitution of split Renilla luciferase. Proc Natl Acad Sci USA 101: 11542–11547.CrossRefGoogle ScholarPubMed
Fields, S., Song, O. (1989). A novel genetic system to detect protein-protein interactions. Nature 340: 245–246.CrossRefGoogle ScholarPubMed
Fields, S., Sternglanz, R. (1994). The two-hybrid system: an assay for protein-protein interactions. Trends Genet 10: 286–292.CrossRefGoogle ScholarPubMed
Ray, P., Pimenta, H., Paulmurugan, R., Berger, F., Phelps, M. E., Iyer, M., Gambhir, S. S. (2002). Noninvasive quantitative imaging of protein-protein interactions in living subjects. Proc Natl Acad Sci USA 99: 3105–3110.CrossRefGoogle ScholarPubMed
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L., Weintraub, H. (1990). The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61: 49–59.CrossRefGoogle ScholarPubMed
Luker, G. D., Sharma, V., Pica, C. M., Dahlheimer, J. L., Li, W., Ochesky, J., Ryan, C. E., Piwnica-Worms, H., Piwnica-Worms, D. (2002). Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci USA 99: 6961–6966.CrossRefGoogle ScholarPubMed
Luker, G. D., Sharma, V., Pica, C. M., Prior, J. L., Li, W., Piwnica-Worms, D. (2003). Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo. Cancer Res 63: 1780–1788.Google ScholarPubMed
Green, L. A., Yap, C. S., Nguyen, K., Barrio, J. R., Namavari, M., Satyamurthy, N., Phelps, M. E., Sandgren, E. P., Herschman, H. R., Gambhir, S. S. (2002). Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Mol Imaging Biol 4: 71–81.CrossRefGoogle ScholarPubMed
Serganova, I., Doubrovin, M., Vider, J., Ponomarev, V., Soghomonyan, S., Beresten, T., Ageyeva, L., Serganov, A., Cai, S., Balatoni, J., Blasberg, R., Gelovani, J. (2004). Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64: 6101–6108.CrossRefGoogle ScholarPubMed
Wang, Y., Iyer, M., Annala, A., Wu, L., Carey, M., Gambhir, S. S. (2006). Noninvasive indirect imaging of vascular endothelial growth factor gene expression using bioluminescence imaging in living transgenic mice. Physiol Genomics 24: 173–180.CrossRefGoogle ScholarPubMed
Dhanasekaran, N. (1998). Cell signaling: an overview. Oncogene 17: 1329–1330.CrossRefGoogle ScholarPubMed
Hunter, T. (2000). Signaling – 2000 and beyond. Cell 100: 113–127.CrossRefGoogle ScholarPubMed
Iyengar, R. (2005). Teaching resources. Introduction: Overview of pathways and networks and GPCR signaling. Sci STKE 2005: tr4.Google ScholarPubMed
Gilman, A. G. et al. (2002). Overview of the alliance for cellular signaling. Nature 420: 703–706.Google ScholarPubMed
Gammon, S. T., Leevy, W. M., Gross, S., Gokel, G. W., Piwnica-Worms, D. (2006). Spectral unmixing of multicolored bioluminescence emitted from heterogeneous biological sources. Anal Chem 78: 1520–1527.CrossRefGoogle ScholarPubMed
Massoud, T. F., Gambhir, S. S. (2007b). Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm. Trends Mol Med 13: 183–191.CrossRefGoogle Scholar
Yarden, Y., Sliwkowski, M. X. (2001). Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2: 127–137.CrossRefGoogle ScholarPubMed
Weinberg, R. A. (2007). The biology of cancer. Garland Science, New York.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×