tailieunhanh - Báo cáo khoa học: Phosphatidylinositol 3,4,5-trisphosphate modulation in SHIP2-deficient mouse embryonic fibroblasts

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)P3 ] in vitro. The present study, which was undertaken to evaluate the impact of SHIP2 on PtdIns(3,4,5)P3 levels, was performed in a mouse embryonic fibroblast (MEF) model using SHIP2 deficient (–⁄–) MEF cells derived from knockout mice. | iFEBS Journal Phosphatidylinositol 3 4 5-trisphosphate modulation in SHIP2-deficient mouse embryonic fibroblasts Daniel Blero1 Jing Zhang1 Xavier Pesesse1 Bernard Payrastre2 Jacques E. Dumont1 Stephane Schurmans3 and Christophe Erneux1 1 Interdisciplinary Research Institute IRIBHM Universite Libre de Bruxelles Belgium 2 INSERM U563 Departement d Oncogenese et Signalization dans les Cellules Hematopoietiques HopitalPurpan Toulouse Cedex France 3 IRIBHM IBMM Gosselies Belgique Keywords inositol 5-phosphatase mouse embryonic fibroblasts phosphatidylinositol 3 4 5-trisphosphate SH2 domain signal transduction. Correspondence C. Erneux Institute of Interdisciplinary Research IRIBHM Campus Erasme Building C 808 Route de Lennik 1070 Brussels Belgium Fax 32 2 555 4655 Tel 32 2 555 4162 E-mail cerneux@ Note D. Blero and J. Zhang contributed equally to this work. Received 27 July 2004 revised 6 February 2005 accepted 21 March 2005 doi 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 P3 in vitro. The present study which was undertaken to evaluate the impact of SHIP2 on PtdIns 3 4 5 P3 levels was performed in a mouse embryonic fibroblast MEF model using SHIP2 deficient MEF cells derived from knockout mice. PtdIns 3 4 5 P3 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 P3 levels we show here that this lipid was significantly upregulated in SHIP2 - - cells but only after short-term . 5-10 min incubation with serum. The difference in PtdIns 3 4 5 P3 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 .

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