Regulation of phosphatidylinositol 3,4,5-trisphosphate 5'-phosphatase activity by insulin
Program in Molecular Medicine and Department of Biochemistry and Molecular Biology
Animals; CHO Cells; Cricetinae; Humans; Insulin; Phosphoric Monoester Hydrolases; Phosphorylation; Precipitin Tests; Receptor, Insulin; Recombinant Proteins
Life Sciences | Medicine and Health Sciences
Polyphosphoinositides are thought to be mediators of cellular signaling pathways as well as regulators of cytoskeletal elements and membrane trafficking events. It has recently been demonstrated that a class of phosphatidylinositol (PI) 3,4,5-P3 5'-phosphatases contains SH2 domains and proline-rich regions, which are present in many signaling proteins. We report here that insulin stimulation of Chinese hamster ovary cells (CHO-T) expressing human insulin receptors causes an 8-10-fold increase in PI 3,4,5-P3 5'-phosphatase activity in anti-phosphotyrosine immunoprecipitates of the cell lysates. This insulin-sensitive polyphosphoinositide 5'-phosphatase did not catalyze dephosphorylation of PI 4,5-P2. No change in 5'-phosphatase activity was detected in insulin receptor or IRS-1 immune complexes in response to insulin. However, insulin treatment of CHO-T cells markedly increased the PI 3,4,5-P3 5'-phosphatase activity associated with Shc and Grb2. The insulin-regulated polyphosphoinositide 5'-phosphatase was not immunoreactive with antibody raised against the recently cloned SHIP 5'-phosphatase reported to associate with Shc and Grb2 in B lymphocytes. These data demonstrate that insulin causes formation of complexes containing a PI 3,4,5-P3 5'-phosphatase, and Shc or Grb2, or both, suggesting an important role of this enzyme in insulin signaling.
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Citation: J Biol Chem. 1996 Nov 22;271(47):29533-6.
The Journal of biological chemistry
Guilherme, Adilson L.; Klarlund, Jes K.; Krystal, Gerald; and Czech, Michael P., "Regulation of phosphatidylinositol 3,4,5-trisphosphate 5'-phosphatase activity by insulin" (1996). Open Access Articles. 793.