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SHIP2: Structure, Function and Inhibition
Author(s) -
Thomas Mark P.,
Erneux Christophe,
Potter Barry V. L.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600541
Subject(s) - dephosphorylation , endocytosis , microbiology and biotechnology , function (biology) , phosphatidylinositol , inositol , phosphatase , chemistry , enzyme , biochemistry , cytoskeleton , phosphorylation , biology , receptor , cell
SHIP2 is a phosphatase that acts at the 5‐position of phosphatidylinositol 3,4,5‐trisphosphate. It is one of several enzymes that catalyse dephosphorylation at the 5‐position of phosphoinositides or inositol phosphates. SHIP2 has a confirmed role in opsismodysplasia, a disease of bone development, but also interacts with proteins involved in insulin signalling, cytoskeletal function (thus having an impact on endocytosis, adhesion, proliferation and apoptosis) and immune system function. The structure of three domains (constituting about 38 % of the protein) is known. Inhibitors of SHIP2 activity have been designed to interact with the catalytic domain with sub‐micromolar IC 50 values: these come from a range of structural classes and have been shown to have in vivo effects consistent with SHIP2 inhibition. Much remains unknown about the roles of SHIP2, and possible future directions for research are indicated.