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

Phospholipase C (PLC)-β₁ and PLC-β₂ 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-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] Gα_q subunits. The C2 domain of PLC-β₁ 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-β₁ and PLC-β₂ provide a surface to which Gα_q subunits can dock, leading to activation of the native protein.