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

• DOI: 10.1128/mcb.18.12.7119
• Publication Date: 2015-10-10T00:34:46Z
• Authors: Serge Roche; J. Downward; Patrick Raynal; Sara A. Courtneidge
• Keywords: 0301 basic medicine; [SDV]Life Sciences [q-bio]; 3T3 Cells; DNA; Fibroblasts; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Precipitin Tests; Antibodies; Androstadienes; Enzyme Activation; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Genes, ras; Animals; Insulin; Receptors, Platelet-Derived Growth Factor; Lysophospholipids; Mitogens; Phosphorylation; Wortmannin; Signal Transduction

We have previously shown that phosphatidylinositol 3-kinase alpha (PI 3-Kalpha) (p85alpha-p110alpha) 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-Kbeta (p85alpha-p110beta) during mitogenesis. By using antibodies specific to p110beta showed expressed NIH 3T3 cells. 3-Kalpha common features: tightly associated with a protein serine kinase phosphorylates p85alpha, 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-Kbeta, suggesting Ras uses other effectors synthesis.