The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin.

摘要: SHIP-2 is a phosphoinositidylinositol 3,4,5 trisphosphate (PtdIns[3,4,5]P3) 5-phosphatase that contains an NH2-terminal SH2 domain, central and COOH-terminal proline-rich domain. negatively regulates insulin signaling. In unstimulated cells, localized in perinuclear cytosolic distribution at the leading edge of cell. Endogenous recombinant to membrane ruffles, which were mediated by proline–rich To identify proteins bind yeast two-hybrid screening was performed, isolated actin-binding protein filamin C. addition, both A B specifically interacted with this assay. coimmunoprecipitated from COS-7 association between these species did not change after epidermal growth factor stimulation. colocalized Z-lines sarcolemma striated muscle sections ruffles although ruffling response reduced cells overexpressing SHIP-2. ruffle localization dependent on binding, as expressed exclusively cytosol filamin-deficient cells. Recombinant regulated PtdIns(3,4,5)P3 levels submembraneous actin stimulation, catalytic activity. Collectively studies demonstrate filamin-dependent critically phosphatidylinositol 3 kinase signaling cytoskeleton.