kringles

Summary

Summary: Triple-looped protein domains linked by disulfide bonds. These common structural domains, so-named for their resemblance to Danish pastries known as kringlers, play a role in binding membranes, proteins, and phospholipids as well as in regulating proteolysis. Kringles are also present in coagulation-related and fibrinolytic proteins and other plasma proteinases.

Top Publications

  1. Tarui T, Akakura N, Majumdar M, Andronicos N, Takagi J, Mazar A, et al. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation. Thromb Haemost. 2006;95:524-34 pubmed
    ..v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist...
  2. Ogorelkova M, Kraft H, Ehnholm C, Utermann G. Single nucleotide polymorphisms in exons of the apo(a) kringles IV types 6 to 10 domain affect Lp(a) plasma concentrations and have different patterns in Africans and Caucasians. Hum Mol Genet. 2001;10:815-24 pubmed
    ..Together, our data suggest that several SNPs in the coding sequence of apo(a) affect Lp(a) levels. This indicates that many SNPs may have subtle effects on the gene product. ..
  3. Kim J, Yu H, Ahn J, Lee H, Hong S, Jung K, et al. Human apolipoprotein(a) kringle V inhibits angiogenesis in vitro and in vivo by interfering with the activation of focal adhesion kinases. Biochem Biophys Res Commun. 2004;313:534-40 pubmed
    ..These results indicate that rhLK8 may be an effective angiogenesis inhibitor both in vitro and in vivo. ..
  4. Yu H, Kim J, Lee H, Ahn J, Lee S, Hong S, et al. Suppression of colorectal cancer liver metastasis and extension of survival by expression of apolipoprotein(a) kringles. Cancer Res. 2004;64:7092-8 pubmed
    ..The present study was performed to evaluate the application of cDNA of LK68 encoding apolipoprotein(a) kringles IV-9, IV-10, and V as possible candidates for gene therapy treatment of this life-threatening disease...
  5. Kim J, Chang J, Yu H, Ahn J, Yum J, Lee S, et al. Inhibition of angiogenesis and angiogenesis-dependent tumor growth by the cryptic kringle fragments of human apolipoprotein(a). J Biol Chem. 2003;278:29000-8 pubmed
    ..Collectively, these results suggest that a truncated apo(a), rhLK68, is a potent anti-angiogenic and anti-tumor molecule. ..
  6. O Neil C, Boffa M, Hancock M, Pickering J, Koschinsky M. Stimulation of vascular smooth muscle cell proliferation and migration by apolipoprotein(a) is dependent on inhibition of transforming growth factor-beta activation and on the presence of kringle IV type 9. J Biol Chem. 2004;279:55187-95 pubmed
    ..The kringle IV type 9-dependent effects of apo(a) on SMC proliferation required the presence of plasminogen, suggesting for the first time that this kringle mediates the ability of apo(a) to inhibit pericellular plasmin formation. ..
  7. Raisler B, Berns K, Grant M, Beliaev D, Hauswirth W. Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1-3 of angiostatin reduce retinal neovascularization. Proc Natl Acad Sci U S A. 2002;99:8909-14 pubmed
  8. Ozhogina O, Trexler M, Banyai L, Llinas M, Patthy L. Origin of fibronectin type II (FN2) modules: structural analyses of distantly-related members of the kringle family idey the kringle domain of neurotrypsin as a potential link between FN2 domains and kringles. Protein Sci. 2001;10:2114-22 pubmed
    ..Since kringles are present in arthropodes, nematodes, and invertebrate chordates as well as in vertebrates, it is suggested that ..
  9. Tarui T, Miles L, Takada Y. Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells. J Biol Chem. 2001;276:39562-8 pubmed
    Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear...

More Information

Publications62

  1. Lanktree M, Anand S, Yusuf S, Hegele R. Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese, and European Caucasians. Circ Cardiovasc Genet. 2010;3:39-46 pubmed publisher
    ..Thus, both SNPs and KIV-2 copy number should be included in future genetic epidemiology studies of Lp(a). ..
  2. Yu H, Ahn J, Lee H, Lee S, Hong S, Yoon Y, et al. Expression of human apolipoprotein(a) kringles in colon cancer cells suppresses angiogenesis-dependent tumor growth and peritoneal dissemination. J Gene Med. 2005;7:39-49 pubmed
    ..These results collectively indicate that a gene therapy strategy using LK68 cDNA is useful for the treatment for both colon tumor growth and peritoneal dissemination. ..
  3. Manosroi J, Tayapiwatana C, Gotz F, Werner R, Manosroi A. Secretion of active recombinant human tissue plasminogen activator derivatives in Escherichia coli. Appl Environ Microbiol. 2001;67:2657-64 pubmed
    ..This finding is an important technological advance in the development of large-scale, bacterium-based tPA production systems. ..
  4. Dahiya M, Rajamohan G, Dikshit K. Enhanced plasminogen activation by staphylokinase in the presence of streptokinase beta/betagamma domains: plasminogen kringles play a role. FEBS Lett. 2005;579:1565-72 pubmed
    ..betagamma domain on Pg activator activity of SAK-Pm complex was reduced greatly (45%) in the presence of isolated kringles of Pg, whereas, kringles did not change cofactor activity of SAK fusion proteins (carrying beta or betagamma ..
  5. Mukhina S, Stepanova V, Traktouev D, Poliakov A, Beabealashvilly R, Gursky Y, et al. The chemotactic action of urokinase on smooth muscle cells is dependent on its kringle domain. Characterization of interactions and contribution to chemotaxis. J Biol Chem. 2000;275:16450-8 pubmed
    ..Together, these findings indicate that uPA-induced chemotaxis is dependent on the binding of the uPA-kringle to the membrane surface of cells and the association of uPA with uPAR. ..
  6. Edelstein C, Shapiro S, Klezovitch O, Scanu A. Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a) biology. J Biol Chem. 1999;274:10019-23 pubmed
    ..cleaves, in vitro, apolipoprotein(a) (apo(a)) in the Asn3518-Val3519 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of the Ile3520-Leu3521 bond, shown previously to be the site of action ..
  7. Ji W, Castellino F, Chang Y, Deford M, Gray H, Villarreal X, et al. Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis. FASEB J. 1998;12:1731-8 pubmed
    ..In this report, we demonstrate for the first time that the kringles of angiostatin play different roles in inhibiting endothelial cell migration, a crucial process in angiogenesis...
  8. Galaup A, Magnon C, Rouffiac V, Opolon P, Opolon D, Lassau N, et al. Full kringles of plasminogen (aa 1-566) mediate complete regression of human MDA-MB-231 breast tumor xenografted in nude mice. Gene Ther. 2005;12:831-42 pubmed
    ..1-566), was dose dependently more potent that AdK1-3(1-354), an adenovirus that expresses only the first three kringles. In contrast to AdK1-3(1-354), a single intratumoral injection of AdK1-5(1-566) into MDA-MB-231 breast human ..
  9. Law R, Caradoc Davies T, Cowieson N, Horvath A, Quek A, Encarnacao J, et al. The X-ray crystal structure of full-length human plasminogen. Cell Rep. 2012;1:185-90 pubmed publisher
    ..The ligand-binding site of KR1 is exposed and likely governs proenzyme recruitment to targets. Furthermore, analysis of our structure suggests that KR5 peeling away from the PAp domain may initiate plasminogen conformational change. ..
  10. Ho Tin Noe B, Rojas G, Vranckx R, Lijnen H, Angles Cano E. Functional hierarchy of plasminogen kringles 1 and 4 in fibrinolysis and plasmin-induced cell detachment and apoptosis. FEBS J. 2005;272:3387-400 pubmed
    Plasmin(ogen) kringles 1 and 4 are involved in anchorage of plasmin(ogen) to fibrin and cells, an essential step in fibrinolysis and pericellular proteolysis...
  11. Shen L, Zhu X, Wang Y, Zeng W, Wu G, Xue H, et al. Secreted human apolipoprotein(a) kringle IV-10 and kringle V inhibit angiogenesis and xenografted tumor growth. Biol Chem. 2008;389:135-41 pubmed publisher
    ..01) against the control tumor cells. From these results, we conclude that human apolipoprotein(a) carboxyl-terminal kringle IV-10-kringle V fusion protein is an effective inhibitor of angiogenesis and angiogenesis-dependent tumor growth. ..
  12. Sumariwalla P, Cao Y, Wu H, Feldmann M, Paleolog E. The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther. 2003;5:R32-9 pubmed
    ..Disruption of synovial angiogenesis is thus a desirable aim of antiarthritic therapies. Protease-activated kringles 1-5 (K1-5) is an angiogenesis inhibitor related to angiostatin...
  13. Belczewski A, Ho J, Taylor F, Boffa M, Jia Z, Koschinsky M. Baboon lipoprotein(a) binds very weakly to lysine-agarose and fibrin despite the presence of a strong lysine-binding site in apolipoprotein(a) kringle IV type 10. Biochemistry. 2005;44:555-64 pubmed
    ..We conclude that presentation of KIV(10) in the context of apo(a) lacking KV may interfere with the ability of KIV(10) to bind to substrates such as fibrin; this paradigm may also be present in other non-human primates. ..
  14. Schmitz V, Raskopf E, Gonzalez Carmona M, Vogt A, Kornek M, Sauerbruch T, et al. Plasminogen derivatives encoding kringles 1-4 and kringles 1-5 exert indirect antiangiogenic and direct antitumoral effects in experimental lung cancer. Cancer Invest. 2008;26:464-70 pubmed publisher
    ..In addition our data supports the recent conclusion that plasminogen derivatives have a dual antitumor mechanism affecting both tumor angiogenesis and tumor cells. ..
  15. Kwak S, Mitra S, Bdeir K, Strassheim D, Park J, Kim J, et al. The kringle domain of urokinase-type plasminogen activator potentiates LPS-induced neutrophil activation through interaction with {alpha}V{beta}3 integrins. J Leukoc Biol. 2005;78:937-45 pubmed
    ..These results demonstrate that the KD of uPA, through interaction with alpha(V)beta(3) integrins, potentiates neutrophil activation. ..
  16. Becker L, Cook P, Koschinsky M. Identification of sequences in apolipoprotein(a) that maintain its closed conformation: a novel role for apo(a) isoform size in determining the efficiency of covalent Lp(a) formation. Biochemistry. 2004;43:9978-88 pubmed
  17. Lee K, Yun S, Kim Y, Yoon Y, Jo E. Adeno-associated virus-mediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice. Hepatology. 2006;43:1063-73 pubmed
    ..Recent studies have identified apolipoprotein(a) [apo(a)] kringles LK68 and LK8 (LKs) as having a potential antiangiogenic and anti-tumor activity, and the current study evaluates ..
  18. Mathews I, Vanderhoff Hanaver P, Castellino F, Tulinsky A. Crystal structures of the recombinant kringle 1 domain of human plasminogen in complexes with the ligands epsilon-aminocaproic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid. Biochemistry. 1996;35:2567-76 pubmed
    ..Ordered solvation effects of the bound AMCHA may contribute to its longer lifetime on Klpg, thereby retarding koff, both effects thus accounting for the higher binding energy of AMCHA as compared to EACA. ..
  19. Cao Y, Ji R, Davidson D, Schaller J, Marti D, Söhndel S, et al. Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells. J Biol Chem. 1996;271:29461-7 pubmed
    ..However, as we also demonstrate, appropriate folding of kringle structures is essential for angiostatin to maintain its full anti-endothelial activity. ..
  20. Bdeir K, Kuo A, Sachais B, Rux A, Bdeir Y, Mazar A, et al. The kringle stabilizes urokinase binding to the urokinase receptor. Blood. 2003;102:3600-8 pubmed
    ..These data demonstrate an important role for the kringle in stabilizing the binding of scuPA to uPAR. ..
  21. Marder V, Manyak S, Gruber T, Goyal A, Moreno G, Hunt J, et al. Haemostatic safety of a unique recombinant plasmin molecule lacking kringles 2-5. Thromb Haemost. 2010;104:780-7 pubmed publisher
    ..We demonstrate that a unique recombinant plasmin mutant, (? K2-5) plasmin, possesses an advantage in hemostatic safety over an equimolar amount of full-length plasmin. ..
  22. Kamstrup P, Tybjaerg Hansen A, Steffensen R, Nordestgaard B. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331-9 pubmed publisher
    ..08 (95% CI, 1.03-1.12). These data are consistent with a causal association between elevated lipoprotein(a) levels and increased risk of MI. ..
  23. Cao Y, Chen A, An S, Ji R, Davidson D, Llinas M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J Biol Chem. 1997;272:22924-8 pubmed
    ..Thus, kringle 5 domain of human plasminogen is a novel endothelial inhibitor that is sufficiently potent to block the growth factor-stimulated endothelial cell growth. ..
  24. Luo X, Tian W, Ni M, Jing X, Lv L, Wang N, et al. Soluble expression of active recombinant human tissue plasminogen activator derivative (K2S) in Escherichia coli. Pharm Biol. 2011;49:653-7 pubmed publisher
    ..These works provided a novel approach for the production of active K2S in E. coli without the requirements of in vitro refolding process, and might establish a significant foundation for the following production of K2S. ..
  25. Rejante M, Llinas M. 1H-NMR assignments and secondary structure of human plasminogen kringle 1. Eur J Biochem. 1994;221:927-37 pubmed
    ..A comparison of secondary structure elements among plasminogen kringles 1 and 4 and tissue-type plasminogen activator kringle 2 suggests that there is variability in the position and ..
  26. Chang P, Chang Y, Wu H, Chang C, Lin C, Wang W, et al. Mutation of human plasminogen kringle 1-5 enhances anti-angiogenic action via increased interaction with integrin alpha(v)beta(3). Thromb Haemost. 2008;99:729-38 pubmed publisher
    ..These results demonstrate that alteration of glycosylation and Lys binding properties could increase the anti-angiogenic action of K(1-5), possibly via enhanced interaction with integrin alpha(v)beta(3) in endothelial cells. ..
  27. Langer C, Tambyrayah B, Nowak Gottl U. Testing for apolipoprotein(a) phenotype using isoelectric focusing and immunoblotting technique. Methods Mol Biol. 2013;992:407-12 pubmed publisher
    ..The number of Kringle 4 repeats correlates negatively with the level of Lp(a) in plasma. The determination of apo(a) phenotype is able to estimate thromboembolic risk due to this risk factor. ..
  28. Langer C, Tambyrayah B, Thedieck S, Nowak Gottl U. Testing for lipoprotein(a) concentration and apolipoprotein(a) phenotypes: method standardization and pediatric reference values. Semin Thromb Hemost. 2011;37:810-3 pubmed publisher
    ..The latter will help to harmonize international pediatric studies and to further evaluate the role of elevated Lp(a) in childhood vascular disease. ..
  29. Lin Y, Tsai M, Lo M, Chang S, Shih Y, Lee M, et al. Evaluation of the antiangiogenic effect of Kringle 1-5 in a rat glioma model. Neurosurgery. 2012;70:479-89; discussion 489-90 pubmed publisher
    ..Kringle 1-5 effectively reduces the growth of malignant gliomas in the rat. Although still far from translation in humans, K1-5 might be a possible future alternative treatment option for patients with gliomas. ..
  30. Lee C, Park K, Sung E, Kim A, Choi J, Kim J, et al. Engineering of a human kringle domain into agonistic and antagonistic binding proteins functioning in vitro and in vivo. Proc Natl Acad Sci U S A. 2010;107:9567-71 pubmed publisher
    ..Our results suggest that the KD scaffold can be used to develop target-specific binding proteins that function as agonists or antagonists toward given target molecules, indicative of their potential use as biotherapeutics. ..
  31. Kumar Y, Vadivel K, Schmidt A, Ogueli G, Ponnuraj S, Rannulu N, et al. Decoy plasminogen receptor containing a selective Kunitz-inhibitory domain. Biochemistry. 2014;53:505-17 pubmed publisher
    ..With its dual function, KD1L17R-KT could serve as a preferred agent for controlling plasminogen activation in pathological processes. ..
  32. Wang M, Zajicek J, Geiger J, Prorok M, Castellino F. Solution structure of the complex of VEK-30 and plasminogen kringle 2. J Struct Biol. 2010;169:349-59 pubmed publisher
    ..Structural analysis and kringle sequence alignments revealed several important features related to exosite binding that provide a structural rationale for the high specificity and affinity of VEK-30 for K2(Pg). ..
  33. Crawford D, Peng Z, Cheng J, Boffelli D, Ahearn M, Nguyen D, et al. LPA and PLG sequence variation and kringle IV-2 copy number in two populations. Hum Hered. 2008;66:199-209 pubmed publisher
    ..Together, these data suggest that LPA SNPs could independently contribute to Lp(a) levels in the general population. ..
  34. Hirschfeldova K, Lipovska D, Skrha P, Ceska R. The apo(a) gene (TTTTA)n promoter polymorphism and its association with variability in exons of the kringle IV types 8 to 10. Clin Chim Acta. 2009;405:39-42 pubmed publisher
    ..The high resolution melting method was used to scan exons of selected kringles for alteration. Linkage disequilibrium and haplotype frequencies were assigned using Arlequine software...
  35. Kang B, Shim B, Lee S, Lee S, Hong Y, Joe Y. Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator. Int J Oncol. 2006;28:361-7 pubmed
    ..coli-derived TK1-2-treated group than in the Pichia-derived TK1-2-treated group. These results suggest that E. coli-derived refolded, non-glycosylated TK1-2 can be used more effectively as an anti-cancer agent. ..
  36. Rejante M, Llinas M. Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1. Eur J Biochem. 1994;221:939-49 pubmed
    ..The computed structure suggests that the epsilon Ahx molecule adopts a kinked conformation when complexed to kringle 1, effectively shortening its dipole length to approximately 0.65 nm. ..
  37. Edelstein C, Italia J, Scanu A. Polymorphonuclear cells isolated from human peripheral blood cleave lipoprotein(a) and apolipoprotein(a) at multiple interkringle sites via the enzyme elastase. Generation of mini-Lp(a) particles and apo(a) fragments. J Biol Chem. 1997;272:11079-87 pubmed
    ..The major cut site was at the interkringle region between apo(a) kringles IV-4 and IV-5 (Ile3520-Leu3521)...
  38. Montesano R, Soriano J, Malinda K, Ponce M, Bafico A, Kleinman H, et al. Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis. Cell Growth Differ. 1998;9:355-65 pubmed
    ..The differential properties of the two HGF/SF isoforms provide a basis for the design of more potent HGF/SF agonists and antagonists. ..
  39. Pantzar M, Ljungh A, Wadstrom T. Plasminogen binding and activation at the surface of Helicobacter pylori CCUG 17874. Infect Immun. 1998;66:4976-80 pubmed
    ..Fragments of plasminogen, kringles 1 to 3, kringle 4, and mini-plasminogen, were also studied as potential inhibitors...
  40. Lu H, Zhang H, Wang Q, Yuan H, He W, Zhao Z, et al. Purification, refolding of hybrid hIFNgamma-kringle 5 expressed in Escherichia coli. Curr Microbiol. 2001;42:211-6 pubmed
    ..The refolded fusion protein, gammaIFN/pk5, has in vitro anti-endothelial cell proliferation activity. ..
  41. Simo J, Joven J, Vilella E, Ribas M, Figuera L, Virgos C, et al. Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship to allele size, plasma lipoprotein(a) concentration, and lysine binding site activity. J Mol Med (Berl). 2001;79:294-9 pubmed
    ..53). This association was not due to linkage disequilibrium with kringle IV repeats. The M75T polymorphism was not associated with the LBS function of apo(a), but it influenced plasma Lp(a) concentration. ..
  42. Zhou Q, Xie J, Xin L, Ye Q, Li Z, Gan R. [Expression and characterization of Kringle 1-5 domains of human plasminogen]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003;35:761-7 pubmed
    ..And rhK1-5 inhibited 47% of the BAEC migration stimulated by bFGF at the concentration of 50 mg/L. rhK1-5 also affected the cell cycle of BAEC and caused G(0)-G(1) arrest at the concentration of 14 mg/L. ..
  43. Dudley A, McKinstry W, Thomas D, Best J, Jenkins A. Removal of endotoxin by reverse phase HPLC abolishes anti-endothelial cell activity of bacterially expressed plasminogen kringle 5. Biotechniques. 2003;35:724-6, 728, 730 passim pubmed
  44. Grishaev A, Llinas M. BACUS: A Bayesian protocol for the identification of protein NOESY spectra via unassigned spin systems. J Biomol NMR. 2004;28:1-10 pubmed
    ..BACUS was validated by tests on experimental NOESY data recorded for the col 2 and kringle 2 domains. ..
  45. Ahn J, Kim J, Yu H, Lee H, Yoon Y. A truncated kringle domain of human apolipoprotein(a) inhibits the activation of extracellular signal-regulated kinase 1 and 2 through a tyrosine phosphatase-dependent pathway. J Biol Chem. 2004;279:21808-14 pubmed
    ..In conclusion, these results indicate that inhibition of endothelial cell migration by rhLK68 may be achieved by interfering with ERK1/2 activation via a protein-tyrosine phosphatase-dependent pathway. ..
  46. Devlin C, Lee S, Kuriakose G, Spencer C, Becker L, Grosskopf I, et al. An apolipoprotein(a) peptide delays chylomicron remnant clearance and increases plasma remnant lipoproteins and atherosclerosis in vivo. Arterioscler Thromb Vasc Biol. 2005;25:1704-10 pubmed
  47. Tolbert W, Daugherty J, Gao C, Xie Q, Miranti C, Gherardi E, et al. A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist. Proc Natl Acad Sci U S A. 2007;104:14592-7 pubmed
    ..This strategy of antagonist design may be applicable for other growth factor receptors by selectively abolishing the receptor activation ability but not the receptor binding of the growth factors. ..
  48. Zhang D, Kaufman P, Gao G, Saunders R, Ma J. Intravitreal injection of plasminogen kringle 5, an endogenous angiogenic inhibitor, arrests retinal neovascularization in rats. Diabetologia. 2001;44:757-65 pubmed
    ..These observations suggest that intravitreal delivery of angiogenic inhibitors could have therapeutic benefits in neovascular diseases of the retina. ..
  49. Wang M, Prorok M, Castellino F. NMR backbone dynamics of VEK-30 bound to the human plasminogen kringle 2 domain. Biophys J. 2010;99:302-12 pubmed publisher
    ..The differences in dynamics observed for kringles with different ligands provide what we believe to be new insights into the interactions responsible for protein-..
  50. Ye Q, Rahman M, Koschinsky M, Jia Z. High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: insights into ligand binding. Protein Sci. 2001;10:1124-9 pubmed
    Apolipoprotein(a) [apo(a)] consists of a series of tandemly repeated modules known as kringles that are commonly found in many proteins involved in the fibrinolytic and coagulation cascades, such as plasminogen and thrombin, respectively...
  51. Trieu V, McConathy W. Functional characterization of T7 and T8 of human apolipoprotein (a). Biochem Biophys Res Commun. 1998;251:356-9 pubmed
    ..1 +/- 1.9 mM, n=3), and more effectively by L-lysine (KI = 2.7 +/- 1.0 mM, n=3) and its analogue, 6-aminohexanoic acid (KI = 0.35 +/- 0.13 mM, n=3). These data point to T7 and T8 as important functional modules of apo(a). ..
  52. Liu L, Boffa M, Koschinsky M. Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system. PLoS ONE. 2013;8:e52287 pubmed publisher
    ..It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis...
  53. Hou W, Chai Y, Wang T, Wang J, Jia Y, Xue L. [Preparation of human recombinant kringle 1-5 and its bioactivity]. Yi Chuan. 2005;27:617-22 pubmed