Phosphoinositide-specific phospholipase C (PLC, EC 3.1.4.11), catalyses the hydrolysis of PIP₂ to IP₃ and 1,2-diacylglycerol, each of which have major second messenger functions. Two domains, X and Y, essential for catalytic activity, are conserved in the different forms of PLC. Isoforms of PLC-β are activated primarily by G protein-coupled receptors through members of the G_q/11 family of G proteins. The receptor-mediated activation of PLC-γ involves their phosphorylation by receptor tyrosine kinases (RTK) in response to activation of a variety of growth factor receptors and immune system receptors. PLC-ε1 may represent a point of convergence of signalling via both G protein-coupled and catalytic receptors. Ca²⁺ ions are required for catalytic activity of PLC isoforms and have been suggested to be the major physiological form of regulation of PLC-δ activity. PLC has been suggested to be activated non-selectively by the small molecule m3M3FBS [2], although this mechanism of action has been questioned [12]. The aminosteroid U73122 has been described as an inhibitor of phosphoinositide-specific PLC [20], although its selectivity among the isoforms is untested and it has been reported to occupy the H₁ histamine receptor [8].

A series of PLC-like proteins (PLCL1, Q15111; PLCL2, Q9UPR0 and PLCH1, Q4KWH8) form a family with PLCδ and PLCζ1 isoforms, but appear to lack catalytic activity.

PLC-δ2 has been cloned from bovine sources [14].

* Key recommended reading is highlighted with an asterisk

Cocco L, Follo MY, Manzoli L, Suh PG. (2015) Phosphoinositide-specific phospholipase C in health and disease. J Lipid Res, 56 (10): 1853-60. [PMID:25821234]

Cockcroft S, Raghu P. (2016) Topological organisation of the phosphatidylinositol 4,5-bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER-PM gap. Biochem J, 473 (23): 4289-4310. [PMID:27888240]

* Filkin SY, Lipkin AV, Fedorov AN. (2020) Phospholipase Superfamily: Structure, Functions, and Biotechnological Applications. Biochemistry (Mosc), 85 (Suppl 1): S177-S195. [PMID:32087059]

* Katan M, Cockcroft S. (2020) Phospholipase C families: Common themes and versatility in physiology and pathology. Prog Lipid Res, 80: 101065. [PMID:32966869]

Litosch I. (2015) Regulating G protein activity by lipase-independent functions of phospholipase C. Life Sci, 137: 116-24. [PMID:26239437]

* Nakamura Y, Fukami K. (2017) Regulation and physiological functions of mammalian phospholipase C. J Biochem, 161 (4): 315-321. [PMID:28130414]

Swann K, Lai FA. (2016) The sperm phospholipase C-ζ and Ca2+ signalling at fertilization in mammals. Biochem Soc Trans, 44 (1): 267-72. [PMID:26862214]

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