G-PROTEIN-COUPLED RECEPTORS AND SIGNALING PATHWAYS REGULATING GROWTH-RESPONSES

Hormones that interact with seven-transmembrane spanning receptors, ge nerally considered to be involved in acute signaling functions, also i nduce longer term effects on gene expression and cell growth, These ge netic and proliferative effects can be induced by activation of recept ors that signal through heterotrimeric GTP-binding proteins (G-protein s) of the G(q) family, pertussis toxin-sensitive G(i)/G(o) proteins, G (s), or G(12)/G(13). Numerous growth-promoting G protein-coupled recep tors activate the low molecular weight G-protein Ras and stimulate mit ogen-activated protein kinase, Recent data suggest that c-Jun NH2-term inal kinase is also activated, possibly through interaction with low m olecular weight G-proteins of the Rho family, Because G protein-couple d receptors lack intrinsic tyrosine kinase activity, the mechanisms by which heterotrimeric G-proteins couple to these kinase cascades remai n to be elucidated, By analogy to growth factor receptors, G protein-c oupled receptors may access these kinase cascades through binding of a dapter proteins or recruitment of cytosolic tyrosine kinases, It is li kely that interactions between multiple signaling pathways are require d for G protein-coupled receptors to propagate signals to the nucleus.