A Function for Phosphatidylinositol 3-Kinase β (p85α-p110β) in Fibroblasts during Mitogenesis: Requirement for Insulin- and Lysophosphatidic Acid-Mediated Signal Transduction

摘要: We have previously shown that phosphatidylinositol 3-kinase a (PI 3-Ka) (p85a-p110a) is required for DNA synthesis induced by various growth factors (S. Roche, M. Koegl, and S. A. Courtneidge, Proc. Natl. Acad. Sci. USA 91:9185‐9189, 1994) in fibroblasts. In the present study, we investigated function of PI 3-Kb (p85a-p110b) during mitogenesis. By using antibodies specific to p110b showed expressed NIH 3T3 cells. 3-Ka common features: tightly associated with protein serine kinase phosphorylates p85a, it interacts Src-middle T antigen complex activated platelet-derived factor (PDGF) receptor fibroblasts vivo, becomes tyrosine phosphorylated after PDGF stimulation. was also Swiss Cos7 cells stimulated lysophosphatidic acid (LPA), mitogen heterotrimeric G protein-coupled receptor. contrast lesser extent these Microinjection neutralizing into quiescent inhibited both insulin LPA but poorly affected signaling. Therefore, plays an important role transmitting mitogenic response some, not all, factors. Finally, show while oncogenic V12Ras type I 3-Ks, could induce absence active 3-Kb, suggesting Ras uses other effectors synthesis. Phosphatidylinositol 3-kinases 3-Ks) belong family enzymes phosphorylate phoshoinositides at 39 position inositol ring, leading formation phos