Selective interaction of the C2 domains of phospholipase C-β(1) and -β(2) with activated Gα(q) subunits: An alternative function for C2-signaling modules

Phospholipase C (PLC)-β(1) and PLC-β(2) are regulated by the G(q) 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-β(1) and PLC-β(2) 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] Gα(q) subunits. The C2 domain of PLC-β(1) effectively suppressed the activation of the intact isozyme by Gα(q)(GTP[γS]), indicating that the C2-Gα(q) interaction may be physiologically relevant. C2 affinity for Gα(q)(GTP[γS]) was reduced when Gα(q) was deactivated to the GDP-bound state. Binding to activated Gα(i1) subunits or to Gβγ subunits was not detected. Also, Gα(q)(GTP[γS]) failed to associate with the C2 domain of PLC-δ, an isozyme that is not activated by Gα(q). These results indicate that the C2 domains of PLC-β(1) and PLC-β(2) provide a surface to which Gα(q) subunits can dock, leading to activation of the native protein.