Selective ineraction of the C2 domains of phospholipase C-β_1 and -βbeta2 with activated Gα_q subunits: An alternative function for C2-signaling modeles

摘要

Phospholipase C(PLC)-β1 and PLC-β2 are regulated by the Gq family of heterotrimeric G proteins and contain C2 domains. These domains are Ca~2+ -binding modules that serve as membrane-attachment motifs in a number of signal transduction proteins. To determine the role that C2 domains play in PLC-β1 and PLC-β2 function, we measured the binding of the isolated C2 domains to membrane bilayers. We found, unexpectedly, that these modules do not bind to membranes but they associate strongly and specifically to activated [guanosine 5'-[γ-thio] triphosphate (GTP[γs])-bound]Gαq subunits. The C2 domain of PLC-β1　effectively suppressed the activation of the intact isozyme by G alpha Gαq(GTP[γS]) was indicating that the C2-G α(GTY[[rS]-bpimd] . reduced when Gαq was deactivated to the GDP-bound state. Binding to activated Gαi1 subunits or to G β gamma subunits was not detected. Also, G αq(GTP[γS]) failed to associate with the C2 domain of PLC-θ, an isozyme that is not activated by G α q, These results indicate that the C2 domains of PLC-β1 and PLC-β 2 provide a surface to which G αq subunits can dock, leading to activation of the native protein.