TY - JOUR
T1 - Activation of phospholipase C-γ by phosphatidylinositol 3,4,5- trisphosphate
AU - Bae, Yun Soo
AU - Cantley, Lloyd G.
AU - Chen, Ching Shih
AU - Kim, Seung Ryul
AU - Kwon, Ki Sun
AU - Rhee, Sue Goo
PY - 1998/2/20
Y1 - 1998/2/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0344653108&partnerID=8YFLogxK
U2 - 10.1074/jbc.273.8.4465
DO - 10.1074/jbc.273.8.4465
M3 - Article
C2 - 9468499
AN - SCOPUS:0344653108
SN - 0021-9258
VL - 273
SP - 4465
EP - 4469
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -