Phospholipase C-gamma (PLCγ)

Phospholipase C-gamma (PLCγ) is a family of phosphoinositide-specific phospholipases, comprising two main isoforms: PLCγ1 and PLCγ2. These enzymes are critical mediators of signal transduction, activated by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (such as BTK and Syk) through their unique SH2 and SH3 domains [1, 4, 10]. Upon activation, PLCγ catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which subsequently trigger calcium release and protein kinase C (PKC) activation [1, 15]. PLCγ1 is ubiquitously expressed and plays a significant role in cell growth, migration, and oncogenesis, while PLCγ2 is primarily restricted to hematopoietic cells and is essential for B-cell and myeloid cell signaling [1, 4, 15]. Mutations in PLCγ2 are clinically significant, as they can lead to autoinflammatory syndromes (PLAID/APLAID) or confer resistance to BTK inhibitors like ibrutinib in B-cell malignancies [4, 7, 13]. Furthermore, PLCγ2 has emerged as a key target in neurodegeneration, with specific variants showing protective effects against Alzheimer's disease by modulating microglial function [13, 16].

Other names

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gammaPhosphoinositide phospholipase C-gammaPLC-gammaPLCG1PLCG2PLC-IIPLC148

Inhibition of the catalytic hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), or disruption of the SH2/SH3 domain-mediated adaptor functions.