Rac, a small guanosine triphosphate–binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces: roles of integrin α2β1
| Autor: | Kaneo Satoh, Mie Kainoh, Toshiaki Tanaka, Naoki Asazuma, Yukio Ozaki, Katsue Suzuki-Inoue, Yutaka Yatomi |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Blood Platelets
Integrins Receptors Collagen Pyridines Immunology Integrin Integrin alpha2 Protein Serine-Threonine Kinases Biology Biochemistry Antibodies Wortmannin Immunoglobulin Fab Fragments chemistry.chemical_compound Platelet Adhesiveness Antigens CD Platelet adhesiveness Humans Src family kinase Enzyme Inhibitors cdc42 GTP-Binding Protein p21-activated kinases Phosphoinositide-3 Kinase Inhibitors Kinase Integrin beta1 Apyrase Cell Biology Hematology Amides rac GTP-Binding Proteins Cell biology Androstadienes Enzyme Activation Pyrimidines p21-Activated Kinases chemistry Rho kinase inhibitor biology.protein Pyrazoles Collagen |
| Zdroj: | Blood. 98:3708-3716 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | In this study, the receptors and signals involved in collagen-induced platelet spreading were examined. It was found that platelet spreading on collagen (presenting a polygon shape with a number of filopodialike projections) was inhibited by the anti-integrin alpha(2) antibody, suggesting the involvement of integrin alpha(2)beta(1) in this process. Studies with a glutathione-S-transferase fusion protein that binds specifically to activated Rac and in vitro p21-activated kinase (PAK) kinase assays revealed that Rac and PAK were activated during this collagen-activated process. Platelet spreading on collagen-coated surfaces was inhibited strongly by PP1 (a Src family kinase inhibitor) or weakly by wortmannin (a phosphatidylinositol 3-kinase [PI3-kinase] inhibitor) but not at all by Y-27632 (a Rho kinase inhibitor). The surfaces coated with anti-integrin alpha(2)beta(1) antibodies also induced platelet spreading (presenting an almost complete round shape) and activation of Rac and PAK, although more slowly than collagen-coated surfaces. The antibody-induced responses were strongly inhibited by PP1 or wortmannin but not by Y-27632. The same concentration of Y-27632 inhibited collagen-induced shape change of platelets in suspension. These findings suggest that Rac and/or PAK activation, but not Rho, may play certain roles in platelet spreading via integrin alpha(2)beta(1) and that Src family kinases and PI3-kinase participate in these processes. Furthermore, the difference between spreading on collagen and the anti-integrin antibody suggests the involvement of other receptor(s) (in addition to the integrin alpha(2)beta(1)) for collagen-induced spreading, the most likely candidate being glycoprotein VI. |
| Databáze: | OpenAIRE |
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