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The role of G-protein coupled receptors and associated proteins in receptor tyrosine kinase signal transduction

Waters, Catherine and Pyne, Susan and Pyne, Nigel J (2004) The role of G-protein coupled receptors and associated proteins in receptor tyrosine kinase signal transduction. Seminars in Cell and Developmental Biology, 15 (3). pp. 309-323. ISSN 1084-9521

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It is well established that stimulation of G-protein coupled receptors (GPCRs) can activate signalling from receptor tyrosine kinases by a process termed transactivation. Indeed, in recent years, it has become apparent that transactivation is a general phenomenon that has been demonstrated for many unrelated GPCRs and receptor tyrosine kinases. In this case the GPCR/G-protein participation is up-stream of the receptor tyrosine kinase. Substantial research has addressed these findings but meanwhile another mechanism of cross talk has been slowly emerging. For over a decade, a growing body of evidence has demonstrated that numerous growth factors use G-proteins and attendant signalling molecules such as beta-arrestins that participate down-stream of the receptor tyrosine kinase to signal to effectors, such as p42/p44 MAPK. This review highlights this novel mechanism of cross talk between receptor tyrosine kinases and GPCRs, which is distinct from growth factor receptor transactivation by GPCRs.