Thrombin

Literature References: Multifunctional serine protease generated at the site of vascular injury from prothrombin, q.v. Key enzyme in the coagulation cascade; converts fibrinogen into fibrin and activates factor XIII, q.v., which cross-links and stabilizes the fibrin polymer. Enhances inflammation and tissue repair via receptor-mediated cellular responses; activates platelets and endothelial cells and stimulates proliferation of fibroblasts and smooth muscle cells. The mature enzyme is glycosylated and consists of two polypeptide chains, designated A and B, covalently linked by a disulfide bridge. Exists in several forms, the largest and most active being the 39 kDa a-thrombin. The human a-thrombin A chain contains 36 amino acids; the B chain contains 259 residues. Purification by conversion from bovine prothrombin: W. H. Seegers et al., J. Biol. Chem. 126, 91 (1938); W. H. Seegers, D. A. McGinty ibid. 146, 511 (1942); H. P. Smith, US 2398077 (1946 to Parke, Davis). Sequence of bovine A chain: S. Magnussen, Biochem. J. 110, 25P (1968). Primary structure of human a-thrombin: R. J. Butkowski et al., J. Biol. Chem. 252, 4942 (1977). Review of structure: M. T. Stubbs, W. Bode, Thromb. Res. 69, 1-58 (1993). Review of cloning, structure and function of thrombin receptors: S. R. Coughlin et al., Cold Spring Harbor Symp. Quant. Biol. 57, 149-154 (1992); C. Tapparelli et al., Trends Pharmacol. Sci. 14, 426-428 (1993). Review of role in hemostasis: J. W. Fenton et al., Hematol. Oncol. Clin. North Am. 7, 1107-1119 (1993); in cell adhesion and proliferation: R. Bar-Shavit et al., Am. J. Resp. Cell Mol. 6, 123-130 (1992); in inflammation and healing and effects in RA: R. Morris et al., Ann. Rheum. Dis. 53, 72-79 (1994).