| First Author | Zhou J | Year | 2018 |
| Journal | Cell Commun Signal | Volume | 16 |
| Issue | 1 | Pages | 98 |
| PubMed ID | 30541554 | Mgi Jnum | J:319310 |
| Mgi Id | MGI:6863640 | Doi | 10.1186/s12964-018-0308-0 |
| Citation | Zhou J, et al. (2018) Tyro3, Axl, and Mertk receptors differentially participate in platelet activation and thrombus formation. Cell Commun Signal 16(1):98 |
| abstractText | BACKGROUND: Previously, several studies have shown that Tyro3, Axl, and Mertk (TAM) receptors participate in platelet activation and thrombosis. However, the role of individual receptors is not fully understood. METHODS: Using single receptor-deficient platelets from TAM knockout mice in the C57BL/6 J strain, we performed a knockout study using single TAM-deficient mice. We treated platelets isolated from TAM knockout mice with the Glycoprotein VI (GPVI) agonists convulxin, poly(PHG), and collagen-related triple-helical peptide (CRP), as well as thrombin for in-vitro experiments. We used a laser-induced cremaster arterial injury model for thrombosis experiments in vivo. RESULTS: Deficiency of the tyrosine kinase receptors, Axl or Tyro3, but not Mertk, inhibited aggregation, spreading, JON/A binding, and P-selectin expression of platelets in vitro. In vivo, platelet thrombus formation was significantly decreased in Axl(-/-) and Tyro3(-/-) mice, but not in Mertk(-/-) mice. Upon stimulation with glycoprotein VI (GPVI) agonists, tyrosine phosphorylation of signaling molecules, including spleen tyrosine kinase (Syk) and phospholipase C-gamma2 (PLCgamma2), was decreased in Axl(-/-) and Tyro3(-/-) platelets, but not in Mertk(-/-) platelets. While platelet aggregation induced by agonists did not differ in the presence or absence of the Gas6 neutralizing antibody, the platelet aggregation was inhibited by anti-Axl or anti-Tyro3 neutralizing antibodies antibody, but not the anti-Mertk antibody. Additionally, the recombinant extracellular domain of Axl or Tyro3, but not that of Mertk, also inhibited platelet aggregation. CONCLUSIONS: These data suggest that Axl and Tyro3, but not Mertk, have an important role in platelet activation and thrombus formation, and mechanistically may do so by a pathway that regulates inside to outside signaling and heterotypic interactions via the extracellular domains of TAMs. |
