A Specific Role of Phosphatidylinositol 3–Kinase γ

• DOI: 10.1083/jcb.152.4.717
• Publication Date: 2002-07-26T16:46:23Z
• Authors: Claire Bony; Serge Roche; Ueno Shuichi; Takehiko Sasaki; Michael A. Crackower; Josef Penninger; Hiroyuki Mano; Michel Pucéat
• Keywords: Wortmannin

Purinergic stimulation of cardiomyocytes turns on a Src family tyrosine kinase–dependent pathway that stimulates PLCγ and generates IP3, breakdown product phosphatidylinositol 4,5–bisphosphate (PIP2). This signaling closely regulates cardiac cell autonomic activity (i.e., spontaneous Ca2+ spiking). PIP2 is phosphorylated 3′ by phosphoinositide 3–kinases (PI3Ks) belong to broad kinase isoforms. The PI3K, 3,4,5–trisphosphate, PLCγ. PI3Ks have emerged as crucial regulators many functions including division, migration, secretion, and, via PLCγ, homeostasis. However, although PI3Kα -β been shown mediate specific in nonhematopoietic cells, such role has not found yet for PI3Kγ. We report neonatal rat cells culture express PI3Kα, -β, -γ. purinergic agonist predominantly activates Both wortmannin LY294002 prevent phosphorylation, membrane translocation well IP3 generation ATP-stimulated cells. Furthermore, an anti-PI3Kγ, but anti-PI3Kβ, injected the prevents effect ATP spiking. A dominant negative mutant PI3Kγ transfected also exerts same action. was observed spiking wild-type PI3Kγ2/2 embryonic stem cell–derived cardiomyocytes. Btk kinase, Tec, induces its association with Tec blocks translocated T-tubes upon anti-PI3Kγ antibody or into latter event. conclude activation step regulation Our data further suggest works concert fully activate cluster kinases provides cardiomyocyte tight thus activity.