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Glucose‐regulated protein 78 ( GRP 78) binds directly to PIP 3 phosphatase SKIP and determines its localization
Author(s) -
Ijuin Takeshi,
Hatano Naoya,
Takenawa Tadaomi
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12353
Subject(s) - biology , phosphatase , insulin receptor , microbiology and biotechnology , protein phosphatase 1 , kinase , insulin , protein phosphatase 2 , inositol , biochemistry , phosphorylation , receptor , endocrinology , insulin resistance
Skeletal muscle and kidney‐enriched inositol polyphosphate phosphatase ( SKIP ), a PIP 3 phosphatase, has been implicated in the regulation of insulin signaling in skeletal muscle. SKIP interacts with Pak1 and glucose‐regulated protein 78 ( GRP 78), both of which are necessary for the regulation of insulin signaling. In this study, we showed that GRP 78 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 GRP 78 and Pak1 competitively bind to SKIP . Taken together, these findings suggest a model by which GRP 78 regulates intracellular localization of SKIP and how SKIP binds to Pak1 on insulin stimulation.