Activated PLCγ breaking loose.

In this issue of Structure, Bunney and colleagues use a combination of NMR, SAXS, crystallography, ITC, and biochemical methods to elucidate, in molecular detail, the sequence of events causing receptor-mediated activation of phospholipase C-γ(1) by protein tyrosine phosphorylation.

Membrane environment exerts an important influence on rac-mediated activation of phospholipase Cγ2.

We performed analyses of the molecular mechanisms involved in the regulation of phospholipase Cγ2 (PLCγ2). We identified several regions in the PLCγ-specific array, γSA, that contribute to autoinhibition in the basal state by occlusion of the catalytic domain. While the activation of PLCγ2 by Rac2 requires stable translocation to the membrane, the removal of the domains required for membrane translocation in the context of an enzyme with impaired autoinhibition generated constitutive, highly active PLC in cells.