Activation of phospholipase C-γ by phosphatidylinositol 3,4,5- trisphosphate

Yun Soo Bae, Lloyd G. Cantley, Ching Shih Chen, Seung Ryul Kim, Ki Sun Kwon, Sue Goo Rhee

Research output: Contribution to journalArticlepeer-review

299 Scopus citations

Abstract

Signal transduction across cell membranes often involves the activation of both phosphatidylinositol (PI)-specific phospholipase C (PLC) and phosphoinositide 3-kinase (PI 3-kinase). Phosphatidylinositol 4,5- bisphosphate (PI(4,5)P2), a substrate for both enzymes, is converted to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) by the action of PI 3-kinase. Here, we show that PI(3,4,5)P3 activates purified PLC-γ isozymes by interacting with their Src homology 2 domains. Furthermore, the expression of an activated catalytic subunit of PI 3-kinase in COS-7 cells resulted in an increase in inositol phosphate formation, whereas platelet-derived growth factor-induced PLC activation in NIH 3T3 cells was markedly inhibited by the specific PI 3-kinase inhibitor LY294002. These results suggest that receptors coupled to PI 3-kinase may activate PLC-γ isozymes indirectly, in the absence of PLC-γ tyrosine phosphorylation, through the generation of PI(3,4,5)P3.

Original languageEnglish
Pages (from-to)4465-4469
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number8
DOIs
StatePublished - 20 Feb 1998

Fingerprint

Dive into the research topics of 'Activation of phospholipase C-γ by phosphatidylinositol 3,4,5- trisphosphate'. Together they form a unique fingerprint.

Cite this