The SH2 domain containing inositol 5-phosphatase SHIP2 controls phosphatidylinositol 3,4,5-trisphosphate levels in CHO-IR cells stimulated by insulin.
The lipid phosphatase SHIP2 (SH2 domain containing inositol 5-phosphatase 2) has recently been shown to be a potent negative regulator of insulin signaling and insulin sensitivity in vivo. We show here that SHIP2 is expressed in Chinese hamster ovary cells overexpressing the insulin receptor (CHO-IR cells) and tyrosine phosphorylated upon insulin stimulation. We show that SHIP2, which is recruited in anti-phosphotyrosine immunoprecipitates in insulin-stimulated cells, accounts for the insulin sensitivity or apparent increase in activity reported by Guilherme et al. (J. Biol. Chem. 271, 29533-29536, 1996). Overexpression of SHIP2 led to a decrease of the insulin-dependent PIP3 production as well as Akt/PKB activation and MAPK stimulation.
Blero
D
D
Interdisciplinary Research Institute (IRIBHN), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, Brussels, 1070, Belgium.
De Smedt
F
F
Pesesse
X
X
Paternotte
N
N
Moreau
C
C
Payrastre
B
B
Erneux
C
C
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015870:Gene Expression; D007328:Insulin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D011518:Proto-Oncogene Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D014443:Tyrosine; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases