Selective activation of effector pathways by brain-specific G protein beta(5)

While multiple G protein beta and gamma subunit isoforms have been identified, the implications of this potential diversity of beta gamma heterodimers for signaling through beta gamma-regulated effector pathways 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-specific 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 contrast, cotransfection of beta(1) but not beta(5) with gamma(2) stimulated the mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) pathways even though the expression of beta(5) in COS cells was evident by immunoblotting. The G protein beta(5) expressed in transfected COS cells was properly folded as its pattern of stable C-terminal 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 that the structural features of the beta gamma complex mediating effector regulation may differ among effectors.