| First Author | Kahner BN | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 7 | Pages | 2449-56 |
| PubMed ID | 17579181 | Mgi Jnum | J:147018 |
| Mgi Id | MGI:3839089 | Doi | 10.1182/blood-2006-11-056069 |
| Citation | Kahner BN, et al. (2007) Hematopoietic lineage cell specific protein 1 (HS1) is a functionally important signaling molecule in platelet activation. Blood 110(7):2449-56 |
| abstractText | 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-family kinase inhibitors. Coimmunoprecipitation experiments revealed that HS1 associates with Syk and phosphatidylinositol 3-kinases. HS1-null mice displayed increased bleeding times and increased time to occlusion in the FeCl(3) 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. |
