C-terminal peptide of thrombospondin-1 induces platelet aggregation through the Fc receptor γ-chain–associated signaling pathway and by agglutination
| Autor: | Mark L. Kahn, Mette Johansen, Denise Best, David Tulasne, Eric J. Brown, Gary A. Koretzky, Naoki Asazuma, Barbi A. Judd, Steve P. Watson |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Platelets
Serotonin Platelet Aggregation Immunology Fc receptor Syk CD47 Antigen Platelet Glycoprotein GPIIb-IIIa Complex Biochemistry Collagen receptor Thrombospondin 1 Mice chemistry.chemical_compound Antigens CD Animals Humans Platelet Amino Acid Sequence Phosphorylation Phosphotyrosine Thrombospondin biology Receptors IgG Tyrosine phosphorylation Cell Biology Hematology Molecular biology Peptide Fragments Platelet Glycoprotein GPIb-IX Complex chemistry biology.protein Signal transduction Carrier Proteins Signal Transduction |
| Zdroj: | Blood. 98:3346-3352 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | A peptide from the C-terminal domain of thrombospondin-1 (Arg-Phe-Tyr-Val-Val-Met-Trp-Lys; known as 4N1-1) has been reported to induce platelet aggregation and to bind to the integrin-associated protein (IAP), which is also known as CD47. In this study, it was discovered that 4N1-1 or its derivative peptide, 4N1K, induces rapid phosphorylation of the Fc receptor (FcR) γ chain, Syk, SLP-76, and phospholipase C γ2 in human platelets. A specific inhibitor of Src family kinases, 4-amino-4-(4-methylphenyl)-7-(t-butyl) pyrazola[3,4-d]pyrimidine, prevented phosphorylation of these proteins, abolished platelet secretion, and reduced aggregation by approximately 50%. A similar inhibition of aggregation to 4N1-1 was obtained in the presence of Arg-Gly-Asp-Ser in mouse platelets deficient in FcR γ chain or SLP-76 and in patients with type I Glanzmann thrombasthenia. These results show that 4N1-1 signals through a pathway similar to that used by the collagen receptor glycoprotein (GP) VI. The αIIbβ3-independent aggregation induced by 4N1-1 was also observed in fixed platelets and platelets from patients with Bernard-Soulier syndrome, which are deficient in GPIbα. Surprisingly, the ability of 4N1-1 to stimulate aggregation and tyrosine phosphorylation was not altered in platelets pretreated with anti-IAP antibodies and in IAP-deficient mice. These results show that the C-terminal peptide of thrombospondin induces platelet aggregation through the FcR γ-chain signaling pathway and through agglutination. The latter pathway is independent of signaling events and does not use GPIbα or αIIbβ3. Neither of these pathways is mediated by IAP. |
| Databáze: | OpenAIRE |
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