Selective activation of effector pathways by brain-specific G protein β2

Abstract

While multiple G protein β γ subunit isoforms have been identified, the implications of this potential diversity of βγ heterodimers for signaling through βγ-regulated effector pathways remains unclear. Further-more the molecular mechanism(s) by which the βγ complex modulates diverse mammalian effector molecules is unknown. Effector signaling by the structurally distinct brain-specific β5 subunit was assessed by transient cotransfection with γ2 in COS cells and compared with β1. Transfection of either β1 or β5 with γ2 stimulated the activity of cotransfected phospholipase C-β2 (PLC-β2), as previously reported. In contrast, cotransfection of β1 but not β5 with γ2 stimulated the mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways even though the expression of β5 in COS cells was evident by immunoblotting. The G protein β5 expressed in transfected COS cells was properly folded as its pattern of stable C-terminal proteolytic fragments was identical to that of native brain β5. The inability of β5 to activate the MAPK and JNK pathways was not overcome by cotransfection with three additional Gγ isoforms. These results suggest it is the Gβ subunit which determines the pattern of downstream signaling by the βγ complex and imply that the structural features of the βγ complex mediating effector regulation may differ among effectors.