title: Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase SKIP and determines its localization.
abstract: Skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP), a PIP3 phosphatase, has been implicated in the regulation of insulin signaling in skeletal muscle. SKIP interacts with Pak1 and glucose-regulated protein 78 (GRP78), both of which are necessary for the regulation of insulin signaling. In this study, we showed that GRP78 directly binds to the SKIP C-terminal homology (SKICH) domain of SKIP and that this binding is necessary for the localization of SKIP at the ER. In addition, in vitro binding analysis showed that GRP78 and Pak1 competitively bind to SKIP. Taken together, these findings suggest a model by which GRP78 regulates intracellular localization of SKIP and how SKIP binds to Pak1 on insulin stimulation.
authors.affiliation: Division of Biochemistry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Chu-o, Kobe, 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ijuin
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Chu-o, Kobe, 650-0017, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hatano
authors.affiliation: Division of Membrane Biology, Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007328:Insulin; D011994:Recombinant Proteins; D054462:p21-Activated Kinases; C471548:SKIP enzyme, human; D010744:Phosphoric Monoester Hydrolases