Activation of the β1 isozyme of phospholipase C by α subunits of the Gq class of G proteins

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Abstract
MANY hormones, neurotransmitters and growth factors, on binding to G protein-coupled receptors or receptors possessing tyrosine kinase activity, increase intracellular levels of the second messengers inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. This is due to activation of phosphoinositide-specific phospho-lipase(s) C (PLC), the isozymes of which are classified into groups, α, β, γ and δ (refs 1, 2). The β, γ and δ groups themselves contain PLC isozymes which have both common and unique structural domains3. Only the γl isozyme has been implicated in a signal transduction mechanism4. This involves association with, and tyrosine phosporylation by, the ligand-bound epidermal growth factor and platelet-derived growth factor receptors5–7, probably by means of the PLC-γl-specific src homology (SH2) domain8. Because EGF receptor-mediated tyrosine phosphorylation of PLC-γ1 stimulates catalytic activity in vitro9 and G proteins have been implicated in the activation of PLC10, we investigated which PLC isozymes are subject to G protein regulation. We have purified11 an activated G protein α subunit that stimulates partially purified phospholipase C and now report that this G protein specifically activates the β1 isozyme, but not the γ1 and δ1 isozymes of phospholipase C. We also show that this protein is related to the Gq class of G protein α subunits12.