SELECTIVE ACTIVATION OF EFFECTOR PATHWAYS BY BRAIN-SPECIFIC G-PROTEINBETA(5)

While multiple G protein beta and gamma subunit isoforms have been ide ntified, the implications of this potential diversity of beta gamma he terodimers for signaling through beta gamma-regulated effector pathway s remains unclear. Furthermore the molecular mechanism(s) by which the beta gamma complex modulates diverse mammalian effector molecules is unknown. Effector signaling by the structurally distinct brain-specifi c beta(5) subunit was assessed by transient cotransfection with gamma( 2) in COS cells and compared with beta(1). Transfection of either beta (1) or beta(5) with gamma(2) stimulated the activity of cotransfected phospholipase C-beta(2) (PLC-beta(2)), as previously reported, In cont rast, cotransfection of beta(1) but not beta(5) with gamma(2) stimulat ed the mitogen-activated protein kinase (MAPK) and c-jun N-terminal ki nase (JNK) pathways even though the expression of beta(5) in COS cells was evident by immunoblotting. The G protein beta(5) expressed in tra nsfected COS cells was properly folded as its pattern of stable C-term inal proteolytic fragments was identical to that of native brain beta( 5). The inability of beta(5) to activate the MAPK and JNK pathways was not overcome by cotransfection with three additional G gamma isoforms . These results suggest it is the G beta subunit which determines the pattern of downstream signaling by the beta gamma complex and imply th at the structural features of the beta gamma complex mediating effecto r regulation may differ among effectors.