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Phospholipase C-gamma is required for agonist-induced Ca2+ entry.

Cell | Nov 15, 2002

We report here that PLC-gamma isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-gamma1 or a lipase-inactive mutant PLC-gamma1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-gamma1 was ineffective. RNA interference to deplete either PLC-gamma1 or PLC-gamma2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-gamma2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-gamma2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-gamma2 or a lipase-inactive PLC-gamma2 mutant. The results indicate a lipase-independent role of PLC-gamma in the physiological agonist-induced activation of Ca2+ entry.

Pubmed ID: 12437926 RIS Download

Mesh terms: Animals | Calcium | Catalysis | Cell Line, Transformed | Humans | Isoenzymes | PC12 Cells | Phospholipase C gamma | RNA, Double-Stranded | RNA, Small Interfering | Rats | Type C Phospholipases

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