1. Phospholipase C-γ Is Required for Agonist-Induced Ca2+ Entry
- Author
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Patterson, Randen L., van Rossum, Damian B., Ford, Diana L., Hurt, Kenneth J., Bae, Sun Sik, Suh, Pann-Ghill, Kurosaki, Tomohiro, Snyder, Solomon H., and Gill, Donald L.
- Subjects
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PHOSPHOLIPASE C , *RNA - Abstract
We report here that PLC-γ isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-γ1 or a lipase-inactive mutant PLC-γ1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-γ1 was ineffective. RNA interference to deplete either PLC-γ1 or PLC-γ2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-γ2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-γ2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-γ2 or a lipase-inactive PLC-γ2 mutant. The results indicate a lipase-independent role of PLC-γ in the physiological agonist-induced activation of Ca2+ entry. [Copyright &y& Elsevier]
- Published
- 2002
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