Kininogen

Factor XI. Factor XI is a Hver-synthesized glycoprotein that circulates in a zymogen form as a dimer. It is converted to its active serine protease form by Factor Xlla in the presence of high molecular weight kininogen. Calcium is not required for this activation step. 

Factor Xlla is a serine protease that activates FXI to FXIa (Fig. 5). This system is not of physiologic relevance since patients with hereditary deficiencies of factor XII, prekallikrein, and high-molecular weight kininogen do not present with bleeding symptoms. 

In humans as well as in other but not all mammalian species, kininogens are modified by posttranslational hydroxylation of a single proline residue of their kinin sequence, i.e. position 3 in bradykinin or position 4 in kallidin. Hydroxylation appears not to affect the specificity, affinity or intrinsic efficacy of the kinins. 

H-kininogen Plasma kallikrein bradykinin (RPPGFSPFR) B2 receptor... 

In rare cases of a systemic release, kinins have the potential to cause severe hypotension. Uncontrolled activation of the contact system (Fig. 3) is thought to trigger a massive formation of kinins under certain pathological conditions [3]. For instance, this situation is seen in patients with underlying diseases such as systemic inflammatory response syndrome (SIRS) due to sepsis or trauma. SIRS progression is accompanied by depletion of contact system factors and low levels of H-kininogen and plasma kallikrein are indicative of a... 

Blais Jr, Marceau F, Rouleau JL et al (2000) The kallikrein-kininogen-kinin system lessons from the quantification of endogenous kinins. Peptides 21 1903—1940... 

Mandle R, Colman R, Kaplan A Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma. Proc Natl Acad Sci USA 1976 73 4179-4183. 

Kerbiriou D, Griffin J Human high molecular 27 weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. J Biol Chem 1979 245 12020-12027. 

Thompson RE, Mandle R Jr, Kaplan AP Studies of 30 binding of prekallikrein and factor XI to high molecular weight kininogen and its light chain. Proc Natl Acad Sci USA 1979 76 4862-4866. 

Tail JF, Fujikawa K Primary structure requirements 31 for the binding of human high molecular weight kininogen to plasma prekallikrein and factor XI. J Biol Chem 1987 262 11651-11656. 

Mori K, Nagasawa S Studies on human high molecular weight (HMW) kininogen. If. Structural change SS of HMW kininogen by the action of human plasma kallikrein. J Biochem 1981 89 1465-1473. 

Reddigari S, Kaplan AP Cleavage of human high-molecular-weight kininogen by purified kaUikreins and upon contact activation of plasma. Blood 1988 71 1334-1340. 

Wiggins RC. Bouma BN. Cochrane CG. Griffin JH Role of high-molecular-weight kininogen in surface-binding and activation of coagulation factor XI and prekallikrein. Proc Natl Acad Sci USA 1977 74 4636-4640. 

Schmaier AH. Silver L. Adams AL, Fischer GC, Munoz PC, Vroman L, et al The effect of high molecular weight kininogen on surface-adsorbed fibrinogen. Thromb Res 1984 33 51-67. 

Schmaier AH, Kuo A, Lundberg D, Murray S, Cines DB The expression of high molecular weight kininogen on human umbilical vein endothelial cells. J Biol Chem 1988 263 16327-16333. 

Reddigari SR, Shibayama Y. Brunnee T. Kaplan AP Human Hageman factor (factor Xll) and high molecular weight kininogen compete for the same binding site on human umbihcal vein endothelial cells. J Biol Chem 1993 268 11982-11987. 

Joseph K, Ghebrehiwet B. Peerschke El. Reid KB. Kaplan AP Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor Xll identity with the receptor that binds to the globular heads of Clq (gClq-R). Proc Natl Acad Sci USA 1996 93 8552-8557. 

Hasan AA, Zisman T. Schmaier AH Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells. Proc Natl Acad Sci USA 1998 95 3615-3620. 

Joseph K, Ghebrehiwet B, Kaplan AP Cytokeratin 1 and gClqR mediate high molecular weight kininogen binding to endothelial cells. Clin Immunol 1999 92 246-255. 

Joseph K, Tholanikunnel BG, Ghebrehiwet B, Kaplan AP Interaction of high molecular weight kininogen binding proteins on endothelial cells. Thromb Haemost 2004 91 61-70. 55... 

Motta G, Rojkjser R, Hasan AA, Cines DB, Schmaier AH High molecular weight kininogen regulates prekallikrein assembly and activation on endothe- 57 lial cells a novel mechanism for contact activation. 

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