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Experimental systems for studying the role of G-protein-coupled receptors in receptor tyrosine kinase signal transduction

Pyne, Nigel J and Waters, Catherine and Moughal, Noreen Akhtar and Sambi, Balwinder and Connell, Michelle and Pyne, Susan (2004) Experimental systems for studying the role of G-protein-coupled receptors in receptor tyrosine kinase signal transduction. Methods in Enzmology, 390. pp. 451-475. ISSN 0076-6879

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Abstract

Early conception of G-protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK) signaling pathways was that each represented distinct and linear modules that converged on downstream targets, such as p42/p44 mitogen-activated protein kinase (MAPK). It has now become clear that this is not the case and that multiple levels of cross-talk exist between both receptor systems at early points during signaling events. In recent years, it has become apparent that transactivation of receptor tyrosine kinases by GPCR agonists is a general phenomenon that has been demonstrated for many unrelated GPCRs and receptor tyrosine kinases. In this case, GPCR/G-protein participation is upstream of the receptor tyrosine kinase. However, evidence now demonstrates that numerous growth factors use G proteins and associated signaling molecules such as beta-arrestins that participate downstream of the receptor tyrosine kinase to signal to effectors, such as p42/p44 MAPK. This article highlights experimental approaches used to investigate this novel mechanism of cross-talk between receptor tyrosine kinases and GPCRs.