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Phosphatidylinositol 3,4,5‐trisphosphate modulation in SHIP2‐deficient mouse embryonic fibroblasts
Author(s) -
Blero Daniel,
Zhang Jing,
Pesesse Xavier,
Payrastre Bernard,
Dumont Jacques E.,
Schurmans Stéphane,
Erneux Christophe
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04672.x
Subject(s) - phosphatidylinositol , downregulation and upregulation , inositol , kinase , biology , microbiology and biotechnology , fibroblast , protein kinase a , endocrinology , medicine , receptor , in vitro , biochemistry , gene
SHIP2, the ubiquitous SH2 domain containing inositol 5‐phosphatase, includes a series of protein interacting domains and has the ability to dephosphorylate phosphatidylinositol 3,4,5‐trisphosphate [PtdIns(3,4,5)P 3 ] in vitro . The present study, which was undertaken to evaluate the impact of SHIP2 on PtdIns(3,4,5)P 3 levels, was performed in a mouse embryonic fibroblast (MEF) model using SHIP2 deficient (–/–) MEF cells derived from knockout mice. PtdIns(3,4,5)P 3 was upregulated in serum stimulated –/– MEF cells as compared to +/+ MEF cells. Although the absence of SHIP2 had no effect on basal PtdIns(3,4,5)P 3 levels, we show here that this lipid was significantly upregulated in SHIP2 –/– cells but only after short‐term (i.e. 5–10 min) incubation with serum. The difference in PtdIns(3,4,5)P 3 levels in heterozygous fibroblast cells was intermediate between the +/+ and the –/– cells. In our model, insulin‐like growth factor‐1 stimulation did not show this upregulation. Serum stimulated phosphoinositide 3‐kinase (PI 3‐kinase) activity appeared to be comparable between +/+ and –/– cells. Moreover, protein kinase B, but not mitogen activated protein kinase activity, was also potentiated in SHIP2 deficient cells stimulated by serum. The upregulation of protein kinase B activity in serum stimulated cells was totally reversed in the presence of the PI 3‐kinase inhibitor LY‐294002, in both +/+ and –/– cells. Altogether, these data establish a link between SHIP2 and the acute control of PtdIns(3,4,5)P 3 levels in intact cells.