Experimental systems for studying the role of G-protein-coupled receptors in receptor tyrosine kinase signal transduction.
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.
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow, Scotland.
Nigel J
NJ
Pyne
Catherine
C
Waters
Noreen Akhtar
NA
Moughal
Balwinder
B
Sambi
Michelle
M
Connell
Susan
S
Pyne
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D037342:Pertussis Toxin / Q000378:metabolism; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000378:metabolism; D000071557:beta-Arrestins
D019390:Arrestins; D020800:Receptor, Nerve Growth Factor; D043562:Receptors, G-Protein-Coupled; D049349:Receptors, Lysosphingolipid; D020032:Tyrphostins; D000071557:beta-Arrestins; C106250:6,7-dimethoxy-3-phenylquinoxaline; D014443:Tyrosine; D037342:Pertussis Toxin; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D020928:Mitogen-Activated Protein Kinases