title: PTEN and SHIP2 regulates PI3K/Akt pathway through focal adhesion kinase.
abstract: Our laboratory has established a novel role of focal adhesion kinase (FAK) in vitro and in vivo, as a positive regulator of insulin signaling pathway. In vitro studies reported tyrosine dephosphorylation of FAK under insulin resistance in C2C12 skeletal muscle cells. A decrease in FAK tyrosine phosphorylation was also observed in skeletal muscle of insulin resistant Sprague-Dawley rats fed on high-fat-diet. Present study was undertaken to explore the cellular mechanism of FAK dephosphorylation under insulin resistance in C2C12 skeletal muscle cells. Here we report that PTEN and SHIP2, the phosphatases widely implicated as negative regulators of insulin signaling, to be responsible for dephosphorylation of FAK. Data propose that under insulin resistance upregulation of PTEN and SHIP2 act through changes in FAK phosphorylation to impair insulin signaling suggesting FAK to be a key mediator of PTEN and SHIP2 in the regulation of insulin signaling. Thus data elucidates a part of molecular mechanism of insulin resistance in skeletal muscle cells.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sec. 67, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Chinmoy Sankar
authors.initials: CS
authors.lastname: Dey
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D000072181:Inositol Polyphosphate 5-Phosphatases; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000072181:Inositol Polyphosphate 5-Phosphatases; D007328:Insulin; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; D019000:Phosphotyrosine; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C487757:Pten protein, mouse; C000606435:Inppl1 protein, mouse; C000606436:Inppl1 protein, rat