IMGT Lexique

Phospholipases C

Phosphatidylinositols are hydrolyzed by phospholipases to generate diacyl-glycerol and inositol phosphates including inositol 1, 4, 5-trisphosphate (IP3). The diacyl-glycerol generated activates protein kinase C (PKC) family members, while IP3 mediates the mobilization of Ca²⁺ from internal stores, resulting in a transient intracellular Ca²⁺ flux. Mammalian cells contain at least ten genes that encode phosphatidylinositol 4, 5-bisphosphate-specific phospholipase C isozymes.

The PLCβ subfamily of enzymes (β1-4) are stringently regulated by G protein-coupled receptors,
The PLCδ isoforms (1-4) are regulated by largely unknown mechanisms, although Ca²⁺may be involved.
The two PLCγ isoforms γ1 and γ 2 are unique in containing two SH2 domains, a SH3 domain, and a PH domain. The SH2 domains allow their recruitment to activated receptor complexes through specific sites of tyrosine phosphorylation on receptor chains. The PH domain is speculated to be important in docking the enzyme to the inner membrane by binding PIP3. The activities of PLCγ 1 and -γ2 are thought to be regulated through direct tyrosine phosphorylation, SH2-mediated conformational changes of the enzyme, or by physical recruitment to the membrane-localized receptor complex.

A wide variety of cytokines, tyrosine kinase receptors, and immunoglobulin superfamily receptors (TcR, BcR and Fc receptors) induce the tyrosine phosphorylation of PLCγ 1 and/or PLCγ2. Both PLCγ1 and PLCγ 2 bind to a major site of tyrosine phosphorylation within the kinase domain of Jak2.

Disruption of the PLCγ1 gene resulted in embryonic lethality during early to midgestation, with death occurring at approximately embryonic day 9. Unlike PLCγ 1, disruption of the PLCγ2 gene does not lead to an embryonic lethality. However, the PLCγ 2-deficient mice have a number of defects in signalling through immunoglobulin receptor superfamily receptors. In B cells, the response to engagement of the IgM antigen receptor is defective, resulting in a phenotype that is very similar to that seen in Btk-deficient mice. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCγ 2 is downstream in Btk/Blnk signalling In addition, collagen-induced platelet aggregation is defective, demonstrating a critical role for PLCγ 2 in signalling through a receptor requiring the FcRγ chain [1].