期刊
BLOOD
卷 110, 期 7, 页码 2449-2456出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-11-056069
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资金
- NHLBI NIH HHS [HL81322, R01 HL060683, T32 HL007777, HL60683, R01 HL080444, HL80444, T32 HL07777, R01 HL081322] Funding Source: Medline
Collagen activates platelets through an intracellular signaling cascade downstream of glycoprotein VI (GPVI). We have investigated the contribution of hematopoietic lineage cell-specific protein 1 (HS1) downstream of GPVI in platelet activation. Stimulation of GPVI leads to tyrosine phosphorylation of HS1, which is blocked by Src-famlly kinase inhibitors. Colimmunoprecipitation experiments revealed that HS1 associates with Syk and phosphatidlylinositol 3-kinases. HS1-null mice displayed increased bleeding times and increased time to occlusion in the FeCl3 in vivo thrombosis model compared with their wild-type littermates. In addition, aggregation and secretion responses were diminished in HS1-null mouse platelets after stimulation of GPVI and protease-activated receptor 4 (PAR-4) agonists compared with wild-type littermate mouse platelets. Finally, Akt phosphorylation was diminished after GPVI or PAR-4 stimulation in platelets from HS1-null mice compared with their wild-type littermates. These results demonstrate that phosphorylation of the HS1 protein occurs downstream of GPVI stimulation and that HS1 plays a significant functional role in platelet activation downstream of GPVI and PARs.
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