Lipid Products of Phosphoinositide 3-Kinase and Phosphatidylinositol 4,5-Bisphosphate Are Both Required for ADP-dependent Platelet Spreading*
| Autor: | Bertrand Perret, Daisy Gironcel, Séverine Roques, Thierry Giacomini, Jean-Michel Heraud, Corinne Albiges-Rizo, Hugues Chap, Monique Breton-Douillon, Claire Racaud-Sultan, Véronique Martel |
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| Přispěvatelé: | Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'études de la différenciation et de l'adhérence cellulaires (LEDAC), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), École nationale supérieure de l'aéronautique et de l'espace (SUPAERO), Ecole Nationale de l'Aéronautique et de l'Espace, Institut Albert Bonniot, This work was supported in part by the Association pour la Recherche sur le Cancer, Paris, and the Conseil Régional Midi-Pyrenées,Toulouse, France, Heraud, Jean-Michel, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Talin MESH: Signal Transduction Indoles Phosphatidylinositols [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biochemistry Maleimides Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound 0302 clinical medicine [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases LY294002 Platelet Enzyme Inhibitors MESH: Blood Platelets Phosphoinositide-3 Kinase Inhibitors MESH: Maleimides [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Indoles 0303 health sciences [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases biology MESH: Phosphatidylinositol 4 5-Diphosphate 3. Good health Cell biology Adenosine Diphosphate Phosphatidylinositol 4 5-bisphosphate MESH: Enzyme Inhibitors 030220 oncology & carcinogenesis [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Pseudopodia Signal transduction Signal Transduction Blood Platelets MESH: Enzyme Activation Morpholines MESH: Morpholines MESH: Cell Adhesion 03 medical and health sciences Cell Adhesion MESH: Phosphatidylinositols Humans Phosphatidylinositol Molecular Biology 030304 developmental biology Phosphoinositide 3-kinase MESH: Humans MESH: Adenosine Diphosphate [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology MESH: Talin Androstadienes Enzyme Activation MESH: Chromones chemistry Chromones [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie MESH: Phosphatidylinositol 3-Kinases MESH: Androstadienes biology.protein [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1998, 273 (28), pp.17817-23. ⟨10.1074/jbc.273.28.17817⟩ Journal of Biological Chemistry, 1998, 273 (28), pp.17817-23. ⟨10.1074/jbc.273.28.17817⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | International audience; We have shown previously that ADP released upon platelet adhesion mediated by IIb 3 integrin triggers accumulation of phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P 2) (Gironcel, D., Racaud-Sultan, C., Payras-tre, B., Haricot, M., Borchert, G., Kieffer, N., Breton, M., and Chap, H. (1996) FEBS Lett. 389, 253–256). ADP has also been involved in platelet spreading. Therefore, in order to study a possible role of phosphoinositide 3-ki-nase in platelet morphological changes following adhesion , human platelets were pretreated with specific phosphoinositide 3-kinase inhibitors LY294002 and wortmannin. Under conditions where PtdIns-3,4-P 2 synthesis was totally inhibited (25 M LY294002 or 100 nM wortmannin), platelets adhered to the fibrinogen matrix , extended pseudopodia, but did not spread. Moreover , addition of ADP to the medium did not reverse the inhibitory effects of phosphoinositide 3-kinase inhibi-tors on platelet spreading. Although synthetic dipalmi-toyl PtdIns-3,4-P 2 and dipalmitoyl phosphatidylinositol 3,4,5-trisphosphate restored only partially platelet spreading, phosphatidylinositol 4,5-bisphosphate (Pt-dIns-4,5-P 2) was able to trigger full spreading of wort-mannin-treated adherent platelets. Following 32 P labeling of intact platelets, the recovery of [ 32 P]PtdIns-4,5-P 2 in anti-talin immunoprecipitates from adherent plate-lets was found to be decreased upon treatment by wort-mannin. These results suggest that the lipid products of phosphoinositide 3-kinase are required but not sufficient for ADP-induced spreading of adherent platelets and that PtdIns-4,5-P 2 could be a downstream messenger of this signaling pathway. |
| Databáze: | OpenAIRE |
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