Phospholipase C-γ is required for agonist-induced Ca2+ entry

Randen L. Patterson, Damian B. Van Rossum, Diana L. Ford, Kenneth J. Hurt, Sun Sik Bae, Pann Ghill Suh, Tomohiro Kurosaki, Solomon H. Snyder, Donald L. Gill

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)529-541
Number of pages13
JournalCell
Volume111
Issue number4
DOIs
StatePublished - Nov 15 2002

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Type C Phospholipases
Programmable logic controllers
Lipase
PC12 Cells
Muscarinic M5 Receptors
src Homology Domains
RNA Interference
Protein Isoforms
B-Lymphocytes
Lymphocytes
Chemical activation
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Patterson, Randen L. ; Van Rossum, Damian B. ; Ford, Diana L. ; Hurt, Kenneth J. ; Bae, Sun Sik ; Suh, Pann Ghill ; Kurosaki, Tomohiro ; Snyder, Solomon H. ; Gill, Donald L. / Phospholipase C-γ is required for agonist-induced Ca2+ entry. In: Cell. 2002 ; Vol. 111, No. 4. pp. 529-541.
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Patterson, RL, Van Rossum, DB, Ford, DL, Hurt, KJ, Bae, SS, Suh, PG, Kurosaki, T, Snyder, SH & Gill, DL 2002, 'Phospholipase C-γ is required for agonist-induced Ca2+ entry', Cell, vol. 111, no. 4, pp. 529-541. https://doi.org/10.1016/S0092-8674(02)01045-0

Phospholipase C-γ is required for agonist-induced Ca2+ entry. / Patterson, Randen L.; Van Rossum, Damian B.; Ford, Diana L.; Hurt, Kenneth J.; Bae, Sun Sik; Suh, Pann Ghill; Kurosaki, Tomohiro; Snyder, Solomon H.; Gill, Donald L.

In: Cell, Vol. 111, No. 4, 15.11.2002, p. 529-541.

Research output: Contribution to journalArticle

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AU - Suh, Pann Ghill

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AU - Snyder, Solomon H.

AU - Gill, Donald L.

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Patterson RL, Van Rossum DB, Ford DL, Hurt KJ, Bae SS, Suh PG et al. Phospholipase C-γ is required for agonist-induced Ca2+ entry. Cell. 2002 Nov 15;111(4):529-541. https://doi.org/10.1016/S0092-8674(02)01045-0