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Pathway Description
Coagulation
Rattus norvegicus
Category:
Protein Pathway
Sub-Categories:
Stress-Activated Signaling
Created: 2018-09-10
Last Updated: 2019-08-16
Blood coagulation can be initiated by either an extrinsic or an intrinsic pathway, resulting in a cascade of serine protease activation that ultimately leads to the formation of thrombin, which converts soluble fibrinogen to an insoluble fibrin clot. The extrinsic, or tissue factor, pathway is initiated upon vascular injury, when the membrane-bound protein tissue factor (TF) comes into contact with factor VII or VIIa in plasma. The TF-VIIa complex is the strongest known activator of the coagulation cascade, and converts factors IX and X to IXa and Xa, respectively. Factors VII, IX, and X are vitamin-K-dependent proteins produced in the liver. In the intrinsic, or contact, pathway, injury exposes collagen to the bloodstream where is binds to factor XII and activates it to XIIa. Factor XIIa converts prekallikrein to kallikrein and factor XI to XIa. Both the extrinsic and intrinsic pathways result in the activation of factor IX to IXa, which forms the 'tenase' complex with factor VIIIa, calcium and phospholipids. This complex converts factor X to Xa and is important in haemostasis. Factor Xa complexes with factor Va (which functions as a non-enzymatic cofactor), calcium and a phospholipid membrane surface to form what is called the prothrombinase complex, which converts prothrombin to thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin polymer, which is stabilized by cross-linking by coagulation factor XIIIa.
References
Coagulation References
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Pubmed: 1993180
Seidah NG, Ladenheim R, Mbikay M, Hamelin J, Lutfalla G, Rougeon F, Lazure C, Chretien M: The cDNA structure of rat plasma kallikrein. DNA. 1989 Oct;8(8):563-74. doi: 10.1089/dna.1989.8.563.
Pubmed: 2598771
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Pubmed: 15489334
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Pubmed: 15057822
Sarkar G, Koeberl DD, Sommer SS: Direct sequencing of the activation peptide and the catalytic domain of the factor IX gene in six species. Genomics. 1990 Jan;6(1):133-43.
Pubmed: 2303254
Frazer DM, Vulpe CD, McKie AT, Wilkins SJ, Trinder D, Cleghorn GJ, Anderson GJ: Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins. Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G931-9. doi: 10.1152/ajpgi.2001.281.4.G931.
Pubmed: 11557513
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Dihanich M, Monard D: cDNA sequence of rat prothrombin. Nucleic Acids Res. 1990 Jul 25;18(14):4251. doi: 10.1093/nar/18.14.4251.
Pubmed: 2377469
Banfield DK, MacGillivray RT: Partial characterization of vertebrate prothrombin cDNAs: amplification and sequence analysis of the B chain of thrombin from nine different species. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2779-83. doi: 10.1073/pnas.89.7.2779.
Pubmed: 1557383
Carney DH, Mann R, Redin WR, Pernia SD, Berry D, Heggers JP, Hayward PG, Robson MC, Christie J, Annable C, et al.: Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides. J Clin Invest. 1992 May;89(5):1469-77. doi: 10.1172/JCI115737.
Pubmed: 1373740
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000586
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