SH2-containing inositol 5-phosphatases 1 and 2 in blood platelets: their interactions and roles in the control of phosphatidylinositol 3,4,5-trisphosphate levels
| Autor: | Christophe Erneux, Sylvie Giuriato, Xavier Pesesse, Evelyne Marion, Cécile Viala, Bernard Payrastre, Stéphane Bodin, Stéphane Schurmans, Takehiko Sasaki, Joseph M. Penninger |
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| Rok vydání: | 2003 |
| Předmět: |
Blood Platelets
Phosphatase Biology Biochemistry src Homology Domains chemistry.chemical_compound Mice Phosphatidylinositol Phosphates Cell Line Tumor Animals Humans Inositol Platelet Phosphatidylinositol Phosphorylation Molecular Biology Cytoskeleton Mice Knockout Src homology domain Phosphatidylinositol (3 4 5)-trisphosphate Inositol Polyphosphate 5-Phosphatases Thrombin Cell Biology Transfection Phosphoric Monoester Hydrolases Cell biology chemistry Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Second messenger system COS Cells Tyrosine Research Article |
| Zdroj: | The Biochemical journal. 376(Pt 1) |
| ISSN: | 1470-8728 |
| Popis: | Src homology domain 2-containing inositol 5-phosphatases 1 and 2 (SHIP1 and SHIP2) are capable of dephosphorylating the second messenger PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) and interacting with several signalling proteins. SHIP1 is essentially expressed in haematopoietic cells, whereas SHIP2, a closely related enzyme, is ubiquitous. In the present study, we show that SHIP1 and SHIP2 are expressed as functional PtdIns(3,4,5)P3 5-phosphatases in human blood platelets and are capable of interacting when these two lipid phosphatases are co-expressed, either naturally (platelets and A20 B lymphoma cells) or artificially (COS-7 cells). Using COS-7 cells transfected with deletion mutants of SHIP2, we demonstrate that the Src homology domain 2 of SHIP2 is the minimal and sufficient protein motif responsible for the interaction between the two phosphatases. These results prompted us to investigate the relative importance of SHIP1 and SHIP2 in the control of PtdIns(3,4,5)P3 levels in platelets using homozygous or heterozygous SHIP1- or SHIP2-deficient mice. Our results strongly suggest that SHIP1, rather than SHIP2, plays a major role in controlling PtdIns(3,4,5)P3 levels in response to thrombin or collagen activation of mouse blood platelets. |
| Databáze: | OpenAIRE |
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