Not so strange bedfellows: G-protein-coupled receptors and Src family kinases

• Published in: Oncogene Vol. 23; no. 48; pp. 7969 - 7978
• Main Authors: Luttrell, Deirdre K, Luttrell, Louis M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.10.2004; Nature Publishing; Nature Publishing Group
• Subjects: Adapter proteins; Adhesion; Animals; Apoptosis; Arrestins - metabolism; beta-Arrestins; Biological and medical sciences; Cell Biology; Cell growth; Cell physiology; Cell proliferation; Cell receptors; Cell structures and functions; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular signal transduction; Cytoskeleton; Fundamental and applied biological sciences. Psychology; G protein-coupled receptors; Genetic aspects; Growth factors; GTP-Binding Proteins - metabolism; Human Genetics; Humans; Internal Medicine; Ion channels; Kinases; Medicine; Medicine & Public Health; Miscellaneous; Molecular and cellular biology; Neurotransmission; Oncology; Phosphorylation; Physiological aspects; Protein Binding; Protein tyrosine kinase; Proteins; Receptors, G-Protein-Coupled - metabolism; review; Signal transduction; Signal Transduction - physiology; Src protein; src-Family Kinases - metabolism; Threonine; Tyrosine; United States; United States > US; mitogen-activated protein kinase; receptor crosstalk; epidermal growth factor; focal adhesion kinase; G-protein-coupled receptor; Enzyme; Transferases; Mitogen-activated protein kinase; Adhesion; Carcinogenesis; Epidermal growth factor; Kinase; Protein-tyrosine kinase; G protein; Biological receptor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208162

Src family nonreceptor tyrosine kinases are an integral component of the signal transduction apparatus employed by growth factor receptor tyrosine kinases. As such, their role in cellular growth control and malignant transformation has been the subject of intensive investigation. In contrast, classical G-protein-coupled receptor (GPCR) signaling involves activation of second messenger-regulated serine/threonine kinases or ion channels, and is primarily involved in neurotransmission and the short-term regulation of intermediary metabolism. Over the past decade, this strictly dichotomous model of transmembrane signaling has been challenged by the discovery that GPCRs also exert control over cellular growth, proliferation, and differentiation, and do so by stimulating tyrosine phosphorylation cascades. Several mechanisms, from the direct association of Src family kinases with GPCRs or receptor-associated proteins, to the transactivation of receptor tyrosine kinases and focal adhesion complexes by G-protein-mediated signals, permit GPCRs to activate Src family kinases. Conversely, Src activity plays a central role in controlling GPCR trafficking and effects on cell proliferation and cytoskeletal rearrangement. It is now clear that GPCRs and Src family kinases do not belong to separate, exclusive clubs. Rather, these strange bedfellows are intimately involved in multilayered forms of crosstalk that influence a host of cellular processes.