Insulin activation of mitogen-activated protein (MAP) kinase and Akt is phosphatidylinositol 3-kinase-dependent in rat adipocytes.
To explore the mechanism of MAP kinase activation in adipocytes, we examined the possible involvement of several candidate signaling proteins. MAP kinase activity was markedly increased 2-4 min after treatment with insulin and declined to basal levels after 20 min. The insulin-dependent tyrosine phosphorylation of IRS-1 in the internal membrane and its association with phosphatidylinositol 3 (PI3) kinase preceded MAP kinase activation. There was little or no tyrosine phosphorylation of Shc or association of Grb2 with Shc or IRS-1. Specific PI3 kinase inhibitors blocked the insulin-mediated activation of MAP kinase. They also decreased the activation of MAP kinase by PMA and EGF but to a much lesser extent. Insulin induced phosphorylation of AKT on serine/threonine residues, and its effect could be blocked by PI3 kinase inhibitors. These results suggest that the insulin-dependent activation of MAP kinase in adipocytes is mediated by the IRS-1/PI3 kinase pathway but not by the Shc/Grb2/SOS pathway.
Liu
H
H
Department of Biochemistry, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts, 02118, USA.
Kublaoui
B
B
Pilch
P F
PF
Lee
J
J
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases