Phospholipase C Gamma 2, Phosphatidylinositol Specific (PLCg2)

Overexpressed wildtype rat Plcg1 or a lipase-inactive mutant Plcg1 each augmented ACE in rat PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of Plcg1 was ineffective. RNA interference to deplete either Plcg1 or Plcg2 in PC12 and rat aortic smooth muscle A7r5 cells inhibited ACE. In chicken DT40 B lymphocytes expressing only Plcg2, overexpressed human muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC2 knockout cells, M5R stimulation of endoplasmic reticulum Ca(2+) store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of rat Plcg2 or a lipase-inactive Plcg2 mutant. The results indicated a lipase-independent role of PLCG in the physiologic agonist-induced activation of Ca(2+) entry.