| Abstract
| - Serotonin (5-HT) is a potent mitogen in many cellstypes, an action which is frequently mediatedthrough pertussis toxin-sensitive G proteins. In the currentstudy, we used pharmacological inhibitorsand dominant negative signaling constructs to delineate elements whichparticipate in the activation ofMAPK, a growth-associated mitogen-activated protein kinase, by human Gprotein-coupled 5-HT1A receptortransfected into CHO-K1 cells in a stable manner. The activationpathway does not directly involvephorbol ester-sensitive protein kinase C types, but does require(i) pertussis toxin-sensitive G proteinβγ-subunits, (ii) a staurosporine- and genistein-sensitiveprotein kinase, (iii) phosphoinositide-3‘-kinaseactivity, (iv) activation of Sos in a multimolecular complex thatcontains p46Shc and p52Shc, and Grb2,(v)the GTPase p21Ras, and (vi) the proteinkinasep74Raf-1.These data demonstrate that the 5-HT1Areceptormediates MAPK activity by convergence upon a common activation pathwaythat is shared with receptortyrosine kinases.
|
