Cross-talk between the platelet-derived growth factor and the insulin signaling pathways in 3T3-L1 adipocytes.
Phosphatidylinositol (PI) 3-kinase is activated by various growth factors such as PDGF (platelet-derived growth factor) and insulin. The aim of the present study was to determine whether PDGF could modulate insulin activation of PI 3-kinase in 3T3-L1 adipocytes. When cells were preincubated for 5-15 min with PDGF, PI 3-kinase activity associated to insulin receptor substrate 1 (IRS 1) in response to insulin was decreased, due to reduced association of the PI 3-kinase p85 subunit with IRS 1. In addition, following this PDGF pretreatment, the tyrosine phosphorylation of IRS 1 in response to insulin and its electrophoretic mobility were diminished. The change in the mobility of IRS 1 could be attributed to PDGF-induced serine/threonine phosphorylation of the protein which was partly inhibited by PI 3-kinase inhibitors. By contrast, epidermal growth factor, which does not stimulate PI 3-kinase, had no effect on the association of PI 3-kinase with IRS 1 in response to insulin. This series of results indicates that the PDGF-induced serine/threonine phosphorylation of IRS 1 could be due to activation of PI 3-kinase pathway. Furthermore, this phosphorylation of IRS 1 is associated with a decrease in its tyrosine phosphorylation by insulin and in its association with the p85 subunit of PI 3-kinase. This study suggests that a cross-talk exists between the different pathways stimulated by PDGF and insulin in intact cells.
Ricort
J M
JM
Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Nice 06107 Cedex 2, France.
Tanti
J F
JF
Van Obberghen
E
E
Le Marchand-Brustel
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007328:Insulin; D007329:Insulin Antagonists; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009025:Morpholines; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin