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

Cell. 2002 Nov 15;111(4):529-41. doi: 10.1016/s0092-8674(02)01045-0.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium
  • Catalysis
  • Cell Line, Transformed
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • PC12 Cells
  • Phospholipase C gamma
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • Rats
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*


  • Isoenzymes
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium