Phosphoinositide-specific phospholipase C (PLC) plays a significant role in transmembrane signaling. In response to extracellular stimuli such as hormones, growth factors and neurotransmitters, PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate two secondary messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). At least four families of PLCs have been identified: PLCb, PLCy, PLCd, and PLCe. Phosphorylation is one of the key mechanisms that regulate the activity of PLC. PLCy is activated by both receptor and non-receptor tyrosine kinases. PLCy forms a complex with EGF and PDGF receptors, which leads to the phosphorylation of PLCy at Tyr771, 783 and 1245. Phosphorylation by Syk at Tyr783 activates the enzymatic activity of PLCy1. PLCy2 is engaged in antigen-dependent signaling in B-cells and collagen-dependent signaling in platelets. Phosphorylation by Btk or Lck at Tyr753, 759, 1197 and 1217 is correlated with PLCy2 activity.