Selective interaction of the C2 domains of phospholipase C-β1 and -β2 with activated Gαq subunits:: An alternative function for C2-signaling modules

Phospholipase C (PLC)-beta(1) and PLC-beta(2) are regulated by the G(q) family of heterotrimeric G proteins and contain C2 domains. These domains are Ca2+-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-beta(1) and PLC-beta(2) function, se 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'-[gamma-thio] triphosphate (GTP[gamma S])-bound] G alpha(q) subunits. The C2 domain of PLC-beta(1) effectively suppressed the activation of the intact isozyme by G alpha(q)(GTP[gamma S]), indicating that the C2-G alpha(q) interaction may be physiologically relevant. C2 affinity for G alpha(q)(GTP[gamma S]) was reduced when G alpha(q) was deactivated to the GDP-bound state. Binding to activated G alpha(i1) subunits or to G beta gamma subunits was not detected. Also, G alpha(q)(GTP[gamma S]) failed to associate with the C2 domain of PLC-delta, an isozyme that is not activated by G alpha(q) These results indicate that the C2 domains of PLC-beta(1) and PLC-beta(2) provide a surface to which G alpha(q) subunits can dock, leading to activation of the native protein.