The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Kringles


High impact information on Kringles

  • The identification of mutations in three distinct domains (containing Frizzled-like, kringle and tyrosine kinase motifs) indicates that these are all essential for ROR2 function [6].
  • The isolated lysine binding site 1 of plasminogen (kringles I-III) retains this binding activity, and binding can be competed for with lysine [7].
  • Lp(a) differs from low-density lipoprotein by the addition of the glycoprotein apolipoprotein(a), a homologue of plasminogen that contains many tandemly repeated units which resemble the fourth kringle domain of plasminogen, and single homologues of its kringle-5 and protease domain [8].
  • Evidence that the fibrinogen binding domain of Apo(a) is outside the lysine binding site of kringle IV-10: a study involving naturally occurring lysine binding defective lipoprotein(a) phenotypes [9].
  • Pretreatment of t-PA with monoclonal antibodies against the EGF/fibronectin finger domain, but not kringle 2 or kringle 1, reduced total binding by 86% [10].

Chemical compound and disease context of Kringles

  • These studies demonstrate that a fully functional EACA-binding kringle from HPg can be expressed and secreted in E. coli, purified by techniques that do not require refolding, and investigated as an independent structural unit [11].
  • Binding of plasmin(ogen) to rat C6 glioma cells is saturable and kringle-domain dependent [12].

Biological context of Kringles

  • A small isoform of SF/HGF encoded by a natural splice variant, which consists of the NH2-terminal hairpin structure and the first two kringle domains but not the protease homology region, induces cell motility but not mitogenesis [13].
  • The proposed homology between the fibronectin type II domain and the Kringle domains of blood clotting and fibrinolytic proteins has been examined in three dimensions by substituting the type II sequence into the bovine prothrombin Kringle 1 tertiary structure, determined by X-ray crystallographical methods at 3.8 A [14].
  • In vivo, tyrosine phosphorylation of p185RON is induced by stimulation with macrophage stimulating protein (MSP), a protease-like factor containing four 'kringle' domains, homologous to HGF [15].
  • In addition, the two kringle regions of t-PA were both coded for by two exons and were cleaved by introns at identical positions [16].
  • NK1 assembles as a homodimer in the asymmetric unit, revealing a novel mode of growth factor dimerization produced by close packing of the N domain of one subunit and the kringle domain of the other, thus bringing the two linkers in close proximity [17].

Anatomical context of Kringles

  • A synergistic efficacy of endothelial inhibition was observed when angiostatin and kringle 5 (K5) were coincubated with capillary endothelial cells [18].
  • Here, we show that the endogenous angiogenesis inhibitor, angiostatin (containing kringle domains 1-4 of plasminogen), serves an anti-inflammatory role, since the kringles 1-3 and its kringle 4 directly interact with leukocyte beta1- and beta2-integrins, respectively [19].
  • Hepatocyte growth factor (HGF) is a heterodimeric molecule composed of the alpha-chain containing the N-terminal hairpin domain, four kringle domains, and the serine protease-like beta-chain [20].
  • To determine the cellular distribution of angiostatin binding in tissues with neovasculature (atherosclerotic coronary arteries), we developed a fusion protein consisting of placental alkaline phosphatase and the first 3 kringles of plasminogen [21].
  • Monoclonal antibodies specific for the growth factor and the kringle 2 domains inhibited the binding of t-PA to liver membranes and the catabolism of t-PA by rat hepatoma cells [22].

Associations of Kringles with chemical compounds

  • It contains a serine protease domain and two types of plasminogen-like kringle domains, one of which is present in 37 copies [23].
  • NK1 is a splice variant of the polypeptide growth factor HGF/SF, which consists of the N-terminal (N) and first kringle (K) domain and requires heparan sulfate or soluble heparin for activity [24].
  • To determine the structural signal required for this differential response, chimeric cDNAs with the propeptide/Gla domains, kringle domain, and serine protease domain exchanged between rFII and hFII were generated (FIIRHH and FIIHRR, FIIRRH and FIIHHR, FIIRHR and FIIHRH) and expressed in both warfarin-treated HEK293 cells and HepG2 cells [25].
  • METHODS AND RESULTS: We constructed ribozyme oligonucleotides containing phosphorothioate DNA- and RNA-targeted kringle 4 of the apo(a) gene that showed 80% homology to plasminogen [26].
  • The kinase domain of this receptor is related to the trk family of neurotrophin receptors, but unlike any previously described receptor, the extracellular region of this Torpedo RTK contains a kringle domain close to the transmembrane domain [27].

Gene context of Kringles


Analytical, diagnostic and therapeutic context of Kringles


  1. Gene transfer of kringle 1-5 suppresses tumor development and improves prognosis of mice with hepatocellular carcinoma. Torimura, T., Ueno, T., Kin, M., Taniguchi, E., Nakamura, T., Inoue, K., Sakata, R., Hashimoto, O., Sakamoto, M., Ohira, H., Kumashiro, R., Sata, M., Yano, H., Kojiro, M., Veitonmaki, N., Cao, Y. Gastroenterology (2006) [Pubmed]
  2. The chemotactic action of urokinase on smooth muscle cells is dependent on its kringle domain. Characterization of interactions and contribution to chemotaxis. Mukhina, S., Stepanova, V., Traktouev, D., Poliakov, A., Beabealashvilly, R., Gursky, Y., Minashkin, M., Shevelev, A., Tkachuk, V. J. Biol. Chem. (2000) [Pubmed]
  3. Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium-derived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5. Gao, G., Li, Y., Gee, S., Dudley, A., Fant, J., Crosson, C., Ma, J.X. J. Biol. Chem. (2002) [Pubmed]
  4. Inhibition of human malignant glioma growth in vivo by human recombinant plasminogen kringles 1-3. Joe, Y.A., Hong, Y.K., Chung, D.S., Yang, Y.J., Kang, J.K., Lee, Y.S., Chang, S.I., You, W.K., Lee, H., Chung, S.I. Int. J. Cancer (1999) [Pubmed]
  5. Prothrombin and its derivatives stimulate motility of melanoma cells. Zhou, H., Gabazza, E.C., Takeya, H., Deguchi, H., Urano, H., Adachi, Y., Suzuki, K. Thromb. Haemost. (1998) [Pubmed]
  6. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Afzal, A.R., Rajab, A., Fenske, C.D., Oldridge, M., Elanko, N., Ternes-Pereira, E., Tüysüz, B., Murday, V.A., Patton, M.A., Wilkie, A.O., Jeffery, S. Nat. Genet. (2000) [Pubmed]
  7. Binding of disease-associated prion protein to plasminogen. Fischer, M.B., Roeckl, C., Parizek, P., Schwarz, H.P., Aguzzi, A. Nature (2000) [Pubmed]
  8. Atherogenesis in transgenic mice expressing human apolipoprotein(a). Lawn, R.M., Wade, D.P., Hammer, R.E., Chiesa, G., Verstuyft, J.G., Rubin, E.M. Nature (1992) [Pubmed]
  9. Evidence that the fibrinogen binding domain of Apo(a) is outside the lysine binding site of kringle IV-10: a study involving naturally occurring lysine binding defective lipoprotein(a) phenotypes. Klezovitch, O., Edelstein, C., Scanu, A.M. J. Clin. Invest. (1996) [Pubmed]
  10. alpha-Fucose-mediated binding and degradation of tissue-type plasminogen activator by HepG2 cells. Hajjar, K.A., Reynolds, C.M. J. Clin. Invest. (1994) [Pubmed]
  11. Construction, expression, and purification of recombinant kringle 1 of human plasminogen and analysis of its interaction with omega-amino acids. Menhart, N., Sehl, L.C., Kelley, R.F., Castellino, F.J. Biochemistry (1991) [Pubmed]
  12. Fibrinogenolytic and fibrinolytic activity of cell-associated plasmin. Humphries, J.E., Vasudevan, J., Gonias, S.L. Arterioscler. Thromb. (1993) [Pubmed]
  13. The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells. Weidner, K.M., Sachs, M., Birchmeier, W. J. Cell Biol. (1993) [Pubmed]
  14. Deriving the generic structure of the fibronectin type II domain from the prothrombin Kringle 1 crystal structure. Holland, S.K., Harlos, K., Blake, C.C. EMBO J. (1987) [Pubmed]
  15. RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. Gaudino, G., Follenzi, A., Naldini, L., Collesi, C., Santoro, M., Gallo, K.A., Godowski, P.J., Comoglio, P.M. EMBO J. (1994) [Pubmed]
  16. The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Ny, T., Elgh, F., Lund, B. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  17. Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding. Chirgadze, D.Y., Hepple, J.P., Zhou, H., Byrd, R.A., Blundell, T.L., Gherardi, E. Nat. Struct. Biol. (1999) [Pubmed]
  18. Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Cao, R., Wu, H.L., Veitonmäki, N., Linden, P., Farnebo, J., Shi, G.Y., Cao, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  19. Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment. Chavakis, T., Athanasopoulos, A., Rhee, J.S., Orlova, V., Schmidt-Wöll, T., Bierhaus, A., May, A.E., Celik, I., Nawroth, P.P., Preissner, K.T. Blood (2005) [Pubmed]
  20. Cooperative interaction between alpha- and beta-chains of hepatocyte growth factor on c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. Matsumoto, K., Kataoka, H., Date, K., Nakamura, T. J. Biol. Chem. (1998) [Pubmed]
  21. Angiostatin binds to smooth muscle cells in the coronary artery and inhibits smooth muscle cell proliferation and migration In vitro. Walter, J.J., Sane, D.C. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  22. Characterization of the binding of plasminogen activators to plasma membranes from human liver. Nguyen, G., Self, S.J., Camani, C., Kruithof, E.K. Biochem. J. (1992) [Pubmed]
  23. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. McLean, J.W., Tomlinson, J.E., Kuang, W.J., Eaton, D.L., Chen, E.Y., Fless, G.M., Scanu, A.M., Lawn, R.M. Nature (1987) [Pubmed]
  24. Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor. Lietha, D., Chirgadze, D.Y., Mulloy, B., Blundell, T.L., Gherardi, E. EMBO J. (2001) [Pubmed]
  25. Structural features of the kringle domain determine the intracellular degradation of under-gamma-carboxylated prothrombin: studies of chimeric rat/human prothrombin. Wu, W., Bancroft, J.D., Suttie, J.W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  26. Novel therapeutic strategy for atherosclerosis: ribozyme oligonucleotides against apolipoprotein(a) selectively inhibit apolipoprotein(a) but not plasminogen gene expression. Morishita, R., Yamada, S., Yamamoto, K., Tomita, N., Kida, I., Sakurabayashi, I., Kikuchi, A., Kaneda, Y., Lawn, R., Higaki, J., Ogihara, T. Circulation (1998) [Pubmed]
  27. Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases. Jennings, C.G., Dyer, S.M., Burden, S.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  28. Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen. DePoli, P., Bacon-Baguley, T., Kendra-Franczak, S., Cederholm, M.T., Walz, D.A. Blood (1989) [Pubmed]
  29. NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo. Jakubczak, J.L., LaRochelle, W.J., Merlino, G. Mol. Cell. Biol. (1998) [Pubmed]
  30. Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration. Pluskota, E., Soloviev, D.A., Plow, E.F. Blood (2003) [Pubmed]
  31. Thermodynamic properties of the binding of alpha-, omega-amino acids to the isolated kringle 4 region of human plasminogen as determined by high sensitivity titration calorimetry. Sehl, L.C., Castellino, F.J. J. Biol. Chem. (1990) [Pubmed]
  32. The lysine binding sites of human plasminogen. Evidence for a critical tryptophan in the binding site of kringle 4. Hochschwender, S.M., Laursen, R.A. J. Biol. Chem. (1981) [Pubmed]
  33. Human plasminogen kringle 4. Crystallization and preliminary diffraction data of two different crystal forms. Mulichak, A.M., Park, C.H., Tulinsky, A., Petros, A.M., Llinás, M. J. Biol. Chem. (1989) [Pubmed]
  34. Quantitative evaluation of the contribution of weak lysine-binding sites present within apolipoprotein(a) kringle IV types 6-8 to lipoprotein(a) assembly. Becker, L., Cook, P.M., Wright, T.G., Koschinsky, M.L. J. Biol. Chem. (2004) [Pubmed]
  35. The interaction of prothrombin with phospholipid membranes is independent of either kringle domain. Kotkow, K.J., Furie, B., Furie, B.C. J. Biol. Chem. (1993) [Pubmed]
WikiGenes - Universities