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Gene Review

KLK1  -  kallikrein 1

Homo sapiens

Synonyms: KLKR, Kallikrein-1, Kidney/pancreas/salivary gland kallikrein, Klk6, Tissue kallikrein, ...
 
 
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Disease relevance of KLK1  

 

Psychiatry related information on KLK1

  • This indicates that normal KLK1 genes, expressed as variants in this RFLP, do not participate in the determination of the limits within which life-style factors may cause blood pressure (BP) changes [6].
 

High impact information on KLK1

  • The importance of the tissue kallikrein system depends upon secretion of the active form of the requisite enzyme in the presence of a source of kininogen [7].
  • In this review, we summarize the recently accumulated knowledge on the human tissue kallikrein gene family, including gene and protein structure, predicted enzymatic activities, tissue expression, hormonal regulation, and alternative splicing [8].
  • As inactivation of the TK gene in the mouse induces endothelial dysfunction, we investigated the vascular, hormonal, and renal phenotypes of carriers of the 53H allele [9].
  • The partial genetic deficiency in TK activity is associated with an inward remodeling of the brachial artery, which is not adapted to a chronic increase in wall shear stress, indicating a new form of arterial dysfunction affecting 5-7% of white people [9].
  • Direct gene delivery of human tissue kallikrein reduces blood pressure in spontaneously hypertensive rats [10].
 

Chemical compound and disease context of KLK1

  • Linkage between KLK1 and the highly polymorphic AC repeat marker within the apolipoprotein C2 (APOC2) locus, which had been established in normal families, was confirmed in myotonic dystrophy families (Z = 4.37, theta = 0.11) [1].
  • Moreover, tissue kallikrein was found in malignant human breast tissue and bradykinin (BK) stimulates the proliferation of immortalised breast cancer cells [11].
  • We investigated the effect of enhanced kallikrein levels on kidney remodeling of DOCA-salt hypertensive rats by systemic delivery of adenovirus containing human tissue kallikrein gene [12].
  • Human and rat prolactinomas contain markedly increased amounts of tissue kallikrein; this is comparatively reduced if patients are pretreated with the dopamine agonist, bromocriptine, before surgery [13].
  • Infection of isolated rat aortic segments with adenovirus containing the human tissue kallikrein gene resulted in a time-dependent secretion of recombinant human tissue kallikrein, and significant increases in nitric oxide (NOx) and guanosine 3',5'-cyclic monophosphate (cGMP) levels post gene transfer [14].
 

Biological context of KLK1

 

Anatomical context of KLK1

 

Associations of KLK1 with chemical compounds

 

Physical interactions of KLK1

  • Kallistatin is a newly identified serine proteinase inhibitor (serpin) which binds to tissue kallikrein and inhibits its enzymatic activity in vitro [26].
  • Seminal plasma collected in the absence of extrinsic inhibitors contained 1.8 +/- 0.6 nM tKK:PCI complex and 4.7 +/- 2.8 nM immunoreactive tKK (mean +/- SD, n = 10), which indicates that about 28% of the total tKK immunoreactivity is forming complexes with PCI [27].
 

Enzymatic interactions of KLK1

 

Co-localisations of KLK1

 

Regulatory relationships of KLK1

 

Other interactions of KLK1

  • The third human tissue kallikrein to be identified, hK2, could be an alternate or complementary marker to kallikrein hK3 (prostate-specific antigen) for prostate diseases [34].
  • Human tissue kallikrein 14 (KLK14) is a novel extracellular serine protease [22].
  • Two members of the human tissue kallikrein (KLK) family of (chymo)tryptic-like serine proteases, KLK5 and KLK7, are implicated in desquamation by digestion of (corneo)desmosomes and inhibition by desquamation-related serine protease inhibitors (SPIs) [35].
  • Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared [36].
  • However, the frequency distribution of KLK1 promoter among VUR patients with or without CRI (A, 50.0% and 67.5%; B, 17.9% and 8.3%; H, 14.3% and 18.3%; K, 17.9% and 5.8%, respectively) was statistically different (P = 0.008) [3].
 

Analytical, diagnostic and therapeutic context of KLK1

References

  1. Predictive diagnosis of myotonic dystrophy with flanking microsatellite markers. Mulley, J.C., Gedeon, A.K., White, S.J., Haan, E.A., Richards, R.I. J. Med. Genet. (1991) [Pubmed]
  2. Association of the tissue kallikrein gene promoter with ESRD and hypertension. Yu, H., Song, Q., Freedman, B.I., Chao, J., Chao, L., Rich, S.S., Bowden, D.W. Kidney Int. (2002) [Pubmed]
  3. Significance of the tissue kallikrein promoter and transforming growth factor-beta1 polymorphisms with renal progression in children with vesicoureteral reflux. Lee-Chen, G.J., Liu, K.P., Lai, Y.C., Juang, H.S., Huang, S.Y., Lin, C.Y. Kidney Int. (2004) [Pubmed]
  4. Kallikrein gene expression in human pituitary tissues. Clements, J.A., Mukhtar, A., Verity, K., Pullar, M., McNeill, P., Cummins, J., Fuller, P.J. Clin. Endocrinol. (Oxf) (1996) [Pubmed]
  5. The human tissue kallikreins (KLKs 1-3) and a novel KLK1 mRNA transcript are expressed in a renal cell carcinoma cDNA library. Rae, F., Bulmer, B., Nicol, D., Clements, J. Immunopharmacology (1999) [Pubmed]
  6. No effect of TaqI polymorphism at the human renal kallikrein (KLK1) locus on normal blood pressure level or variability. Berge, K.E., Berg, K. Clin. Genet. (1993) [Pubmed]
  7. Kinin formation: mechanisms and role in inflammatory disorders. Proud, D., Kaplan, A.P. Annu. Rev. Immunol. (1988) [Pubmed]
  8. The new human tissue kallikrein gene family: structure, function, and association to disease. Yousef, G.M., Diamandis, E.P. Endocr. Rev. (2001) [Pubmed]
  9. Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans. Azizi, M., Boutouyrie, P., Bissery, A., Agharazii, M., Verbeke, F., Stern, N., Bura-Rivière, A., Laurent, S., Alhenc-Gelas, F., Jeunemaitre, X. J. Clin. Invest. (2005) [Pubmed]
  10. Direct gene delivery of human tissue kallikrein reduces blood pressure in spontaneously hypertensive rats. Wang, C., Chao, L., Chao, J. J. Clin. Invest. (1995) [Pubmed]
  11. Mitogenic signalling by B2 bradykinin receptor in epithelial breast cells. Greco, S., Muscella, A., Elia, M.G., Romano, S., Storelli, C., Marsigliante, S. J. Cell. Physiol. (2004) [Pubmed]
  12. Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats. Xia, C.F., Bledsoe, G., Chao, L., Chao, J. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  13. Tissue kallikrein is associated with prolactin-secreting cells within human growth hormone-secreting adenomas. Jones, T.H., Figueroa, C.D., Smith, C.M., Cullen, D.R., Bhoola, K.D. J. Endocrinol. (1992) [Pubmed]
  14. Adenovirus-mediated kallikrein gene transfer inhibits neointima formation via increased production of nitric oxide in rat artery. Murakami, H., Miao, R.Q., Chao, L., Chao, J. Immunopharmacology (1999) [Pubmed]
  15. Molecular cloning of the human kallikrein 15 gene (KLK15). Up-regulation in prostate cancer. Yousef, G.M., Scorilas, A., Jung, K., Ashworth, L.K., Diamandis, E.P. J. Biol. Chem. (2001) [Pubmed]
  16. The evolution of the glandular kallikrein locus: identification of orthologs and pseudogenes in the cotton-top tamarin. Olsson, A.Y., Valtonen-André, C., Lilja, H., Lundwall, A. Gene (2004) [Pubmed]
  17. Human glandular Kallikrein genes: genetic and physical mapping of the KLK1 locus using a highly polymorphic microsatellite PCR marker. Richards, R.I., Holman, K., Shen, Y., Kozman, H., Harley, H., Brook, D., Shaw, D. Genomics (1991) [Pubmed]
  18. Tissue kallikrein KLK1 is expressed de novo in endothelial cells and mediates relaxation of human umbilical veins. Dedio, J., Wiemer, G., Rütten, H., Dendorfer, A., Schölkens, B.A., Müller-Esterl, W., Wohlfart, P. Biol. Chem. (2001) [Pubmed]
  19. Expression of the kallikrein gene family in normal and Alzheimer's disease brain. Shimizu-Okabe, C., Yousef, G.M., Diamandis, E.P., Yoshida, S., Shiosaka, S., Fahnestock, M. Neuroreport (2001) [Pubmed]
  20. Glandular kallikrein gene expression in the human uterus. Clements, J., Mukhtar, A., Ehrlich, A., Yap, B. Braz. J. Med. Biol. Res. (1994) [Pubmed]
  21. Porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 gene expression. Fernando, S.C., Buck, J.S., Ashworth, M.D., Ross, J.W., Geisert, R.D., Desilva, U. Reproduction (2006) [Pubmed]
  22. Expression and Functional Characterization of the Cancer-related Serine Protease, Human Tissue Kallikrein 14. Borgoño, C.A., Michael, I.P., Shaw, J.L., Luo, L.Y., Ghosh, M.C., Soosaipillai, A., Grass, L., Katsaros, D., Diamandis, E.P. J. Biol. Chem. (2007) [Pubmed]
  23. Specificity of human tissue kallikrein towards substrates containing Phe-Phe pair of amino acids. Pimenta, D.C., Chao, J., Chao, L., Juliano, M.A., Juliano, L. Biochem. J. (1999) [Pubmed]
  24. Kininogenase activity of prostate-derived human glandular kallikrein (hK2) purified from seminal fluid. Charlesworth, M.C., Young, C.Y., Miller, V.M., Tindall, D.J. J. Androl. (1999) [Pubmed]
  25. Kallistatin: a novel human tissue kallikrein inhibitor. Purification, characterization, and reactive center sequence. Zhou, G.X., Chao, L., Chao, J. J. Biol. Chem. (1992) [Pubmed]
  26. Cellular localization of tissue kallikrein and kallistatin mRNAs in human kidney. Chen, L.M., Song, Q., Chao, L., Chao, J. Kidney Int. (1995) [Pubmed]
  27. Complexes of tissue kallikrein with protein C inhibitor in human semen and urine. España, F., Fink, E., Sanchez-Cuenca, J., Gilabert, J., Estellés, A., Witzgall, K. Eur. J. Biochem. (1995) [Pubmed]
  28. Biochemistry, regulation and potential function of kallistatin. Chao, J., Chao, L. Biol. Chem. Hoppe-Seyler (1995) [Pubmed]
  29. Hydrolysis of somatostatin by human tissue kallikrein after the amino acid pair phe-Phe. Pimenta, D.C., Juliano, M.A., Juliano, L. Biochem. J. (1997) [Pubmed]
  30. Characterization of a tissue kallikrein in human prolactin-secreting adenomas. Jones, T.H., Figueroa, C.D., Smith, C., Cullen, D.R., Bhoola, K.D. J. Endocrinol. (1990) [Pubmed]
  31. Elevated tissue kallikrein activity in airway secretions from patients with tracheobronchitis associated with prolonged mechanical ventilation. O'Riordan, T.G., Weinstein, M.D., Abraham, W.M., Forteza, R. Lung (2003) [Pubmed]
  32. Possible identity of kallikrein binding protein with protein C inhibitor. Ecke, S., Geiger, M., Resch, I., Jerabek, I., Maier, M., Binder, B.R. Agents Actions Suppl. (1992) [Pubmed]
  33. Transgenic activation of the kallikrein-kinin system inhibits intramyocardial inflammation, endothelial dysfunction and oxidative stress in experimental diabetic cardiomyopathy. Tschöpe, C., Walther, T., Escher, F., Spillmann, F., Du, J., Altmann, C., Schimke, I., Bader, M., Sanchez-Ferrer, C.F., Schultheiss, H.P., Noutsias, M. FASEB J. (2005) [Pubmed]
  34. Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2. Bourgeois, L., Brillard-Bourdet, M., Deperthes, D., Juliano, M.A., Juliano, L., Tremblay, R.R., Dubé, J.Y., Gauthier, F. J. Biol. Chem. (1997) [Pubmed]
  35. A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. Borgoño, C.A., Michael, I.P., Komatsu, N., Jayakumar, A., Kapadia, R., Clayman, G.L., Sotiropoulou, G., Diamandis, E.P. J. Biol. Chem. (2007) [Pubmed]
  36. Vitronectin modulates glycosaminoglycan dependent reactions of protein C inhibitor. Seiffert, D., Geiger, M., Ecke, S., Binder, B.R. Thromb. Haemost. (1992) [Pubmed]
  37. Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium. Clements, J., Mukhtar, A. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  38. The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction. Chao, J., Bledsoe, G., Yin, H., Chao, L. Biol. Chem. (2006) [Pubmed]
  39. Tissue kallikrein is synthesized and secreted by human vascular endothelial cells. Yayama, K., Kunimatsu, N., Teranishi, Y., Takano, M., Okamoto, H. Biochim. Biophys. Acta (2003) [Pubmed]
 
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