Phospholipase C-gamma (PLC-γ) (PLC-γ)

Phospholipase C-gamma (PLC-γ) is a family of enzymes, including the isoforms PLC-γ1 and PLC-γ2, that serve as critical hubs in intracellular signal transduction [6, 8]. These enzymes are activated by tyrosine phosphorylation downstream of various cell surface receptors, such as receptor tyrosine kinases (RTKs) and immune receptors like the B-cell and T-cell receptors [3, 5, 9]. Once activated, PLC-γ catalyzes the hydrolysis of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) into two key second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) [1, 5, 19]. IP3 facilitates the release of calcium from intracellular stores, while DAG activates protein kinase C (PKC), together regulating processes like cell proliferation, differentiation, and immune activation [1, 3, 8]. PLC-γ1 is ubiquitously expressed and essential for embryonic development, whereas PLC-γ2 is primarily restricted to hematopoietic cells and is vital for immune cell function [8, 15, 22]. Dysregulation of PLC-γ signaling is implicated in several pathologies, including various cancers (e.g., T-cell lymphomas), inflammatory disorders, and neurodegenerative diseases like Alzheimer's [7, 10, 20]. Notably, gain-of-function mutations in PLCG2 are a major driver of resistance to Bruton's tyrosine kinase (BTK) inhibitors in chronic lymphocytic leukemia [18, 20, 24]. Consequently, PLC-γ is an attractive therapeutic target, with research focusing on developing selective small-molecule inhibitors and allosteric modulators to treat cancer and autoimmune conditions [7, 16, 19].

Other names

PLC-gammaPLCGPLC-IIPLC1481-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)