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Gene Review

Klk1  -  kallikrein 1

Rattus norvegicus

Synonyms: Gamma-NGF, Kallikrein-1, Klk-1, Klk1b3, Klk1c1, ...
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Disease relevance of Ngfg

  • Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat [1].
  • The serine proteinase tissue kallikrein has been previously demonstrated in several human adenocarcinomas, and we presently report the localization of immunoreactive kallikrein and its mRNA in pancreatic adenocarcinoma [2].
  • FE999024 (20 micromol kg(-1)) largely inhibited increased tissue kallikrein-like activity in the pancreas during acute pancreatitis and also strongly attenuated influx of plasma kallikrein into the tissue [3].
  • In all mammals investigated so far, an amount of 0.1 - 1 biological unit (KU) of hog pancreatic kallikrein per kg body weight injected intravenously caused a fast reduction in blood pressure with one exception, the rat [4].
  • The present study shows that tissue kallikrein is present in rat pancreas as a proenzyme that can be converted by autolysis to a 38 000 Da active enzyme [5].

High impact information on Ngfg


Biological context of Ngfg


Anatomical context of Ngfg


Associations of Ngfg with chemical compounds

  • The content of kallikrein, determined by an RIA highly specific for rK1 (true tissue kallikrein), rose in ovariectomized rats with estradiol supplementation (0.28 +/- 0.03 to 0.44 +/- 0.05 ng/mg) and decreased with progesterone (0.13 +/- 0.02 ng/mg; n = 15; p < 0.001) [13].
  • The amino-terminal sequences of the first 25 residues of RUK resemble the reported sequence for true kallikrein and share 80% identity with rat submandibular gland (RSMG) kallikrein-like serine protease [17].
  • However, whereas alpha-stimulation produced a significant decrease in kallikrein concentration in the stimulated SMG, beta-adrenergic and theophylline stimulation produced no significant changes in tissue kallikrein [18].
  • OBJECTIVE: We have reported that bradykinin (BK) excretion is increased in severely diabetic rats, independent of the activity of the main renal kinin-forming enzyme, true kallikrein (KLK) [19].
  • Using a cloned complementary DNA (cDNA) to rat pancreatic kallikrein (pcXP39) for hybridization histochemistry, and both Northern and dot blot analysis, we studied expression of the kallikrein gene in steroid-treated control animals, and in three strains of genetically hypertensive rats [20].

Regulatory relationships of Ngfg


Other interactions of Ngfg

  • Compared to the coding sequence of pancreatic kallikrein, 12 nucleotides have been deleted in exon 3 of the RSKG-50 gene [23].
  • Peptide substrates with intramolecularly quenched fluorescence that reproduce the rat kininogen sequences at both ends of the bradykinin moiety were synthesized and used to investigate the kinin-releasing properties of five rat tissue kallikreins (rK1, rK2, rK7, rK9, rK10) [24].
  • The presence of GalNAc in addition to GlcNAc, Fuc, Gal, and Man, in sugar chains of rK1 was confirmed by high pH anion exchange chromatography following acid hydrolysis [25].
  • These results suggest that there are two kinin-generating systems in rat myocardium comprising T-kininogen/T-kininogenase and L-kininogen/true kallikrein respectively, and that the former may be relatively important in inflammatory diseases or conditions in which cAMP levels increase in cardiomyocytes [26].
  • We found only a slow and weak reduction of rat blood pressure after injection of 100 KU hog pancreatic kallikrein per rat, when the endogenous kininases had been previously inactivated by the kininase II inhibitor captopril [4].

Analytical, diagnostic and therapeutic context of Ngfg


  1. Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat. Iwai, N., Yasui, N., Naraba, H., Tago, N., Yamawaki, H., Sumiya, H. Hypertension (2005) [Pubmed]
  2. A synthetic tissue kallikrein inhibitor suppresses cancer cell invasiveness. Wolf, W.C., Evans, D.M., Chao, L., Chao, J. Am. J. Pathol. (2001) [Pubmed]
  3. Involvement of tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenous kinins in acute pancreatitis in rats. Griesbacher, T., Rainer, I., Tiran, B., Evans, D.M. Br. J. Pharmacol. (2002) [Pubmed]
  4. Effect of hog pancreatic kallikrein on blood pressure in rats. Schack, L., Dietl, T. Hoppe-Seyler's Z. Physiol. Chem. (1982) [Pubmed]
  5. Immunological analysis of rat pancreatic prokallikrein activation. Woodley, C.M., Chao, J., Chao, L. Biochim. Biophys. Acta (1985) [Pubmed]
  6. Pancreatic kallikrein gene expression: effects of glucocorticoids in vivo and in vitro. Rosewicz, S., Logsdon, C.D. Gastroenterology (1989) [Pubmed]
  7. Rat pancreatic kallikrein mRNA: nucleotide sequence and amino acid sequence of the encoded preproenzyme. Swift, G.H., Dagorn, J.C., Ashley, P.L., Cummings, S.W., MacDonald, R.J. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  8. Tissue-specific developmental expression of the kallikrein gene family in the rat. Clements, J.A., Matheson, B.A., Funder, J.W. J. Biol. Chem. (1990) [Pubmed]
  9. Organization and expression of the rat kallikrein gene family. Wines, D.R., Brady, J.M., Pritchett, D.B., Roberts, J.L., MacDonald, R.J. J. Biol. Chem. (1989) [Pubmed]
  10. Inhibition of rat tissue kallikrein gene family members by rat kallikrein-binding protein and alpha 1-proteinase inhibitor. Serveau, C., Moreau, T., Zhou, G.X., ElMoujahed, A., Chao, J., Gauthier, F. FEBS Lett. (1992) [Pubmed]
  11. Identification and structure of the rat true tissue kallikrein gene expressed in the kidney. Inoue, H., Fukui, K., Miyake, Y. J. Biochem. (1989) [Pubmed]
  12. Tissue-specific expression of kallikrein-related genes in the rat. Ashley, P.L., MacDonald, R.J. Biochemistry (1985) [Pubmed]
  13. Estrogen and luminal stimulation of rat uterine kallikrein. Corthorn, J., Figueroa, C., Valdés, G. Biol. Reprod. (1997) [Pubmed]
  14. Tissue kallikrein in the rat pineal gland: an immunocytochemical study. Fujieda, H., Sato, T., Wake, K., Takaoka, M., Morimoto, S. J. Pineal Res. (1993) [Pubmed]
  15. Kallikrein rK10-induced kinin-independent, direct activation of NO-formation and relaxation of rat isolated aortic rings. Wassdal, I., Hull, R., Gerskowitch, V.P., Berg, T. Br. J. Pharmacol. (1995) [Pubmed]
  16. Tissue kallikrein clearance by the liver--effect of plasma components on kallikrein uptake by cultured rat hepatocytes. Aoki, K., Kamada, M., Ikekita, M., Kizuki, K., Moriya, H. Agents Actions Suppl. (1992) [Pubmed]
  17. Purification of rat urinary kallikrein: comparative studies with rat submandibular gland kallikrein-like serine protease. Bedi, G.S. Prep. Biochem. (1992) [Pubmed]
  18. Release of tonin and of kallikrein by perfused rat submaxillary gland. Garcia, R., Thibault, G., Gutkowska, J., Genest, J. Am. J. Physiol. (1983) [Pubmed]
  19. Renal expression of two rat kallikrein genes under diabetic conditions. Tschöpe, C., Yu, M., Reinecke, A., Csikos, T., Hilgenfeldt, U., Pesquero, J.B., Ritz, E., Unger, T. J. Hypertens. (1997) [Pubmed]
  20. Expression of the renal kallikrein gene in mineralocorticoid-treated and genetically hypertensive rats. Fuller, P.J., Clements, J.A., Nikolaidis, I., Hiwatari, M., Funder, J.W. J. Hypertens. (1986) [Pubmed]
  21. Intestinal absorption of glandular kallikrein in the rat. Overlack, A., Scicli, A.G., Carretero, O.A. Am. J. Physiol. (1983) [Pubmed]
  22. Insulin potentiates cholecystokinin (CCK)-induced secretion of pancreatic kallikrein. Berg, T., Johansen, L., Brekke, I.B. Acta Physiol. Scand. (1985) [Pubmed]
  23. Characterization of genes encoding rat tonin and a kallikrein-like serine protease. Shai, S.Y., Woodley-Miller, C., Chao, J., Chao, L. Biochemistry (1989) [Pubmed]
  24. Kininogen-derived fluorogenic substrates for investigating the vasoactive properties of rat tissue kallikreins--identification of a T-kinin-releasing rat kallikrein. El Moujahed, A., Brillard-Bourdet, M., Juliano, M.A., Moreau, T., Chagas, J.R., Gutman, N., Prado, E.S., Gauthier, F. Eur. J. Biochem. (1997) [Pubmed]
  25. Differences in the glycosylation of rat submandibular kallikreins. Zhang, X.S., Proctor, G.B., Garrett, J.R., Shori, D.K., Carpenter, G.H. Glycoconj. J. (1996) [Pubmed]
  26. Expression of kininogen, kallikrein and kinin receptor genes by rat cardiomyocytes. Yayama, K., Nagaoka, M., Takano, M., Okamoto, H. Biochim. Biophys. Acta (2000) [Pubmed]
  27. The immunological similarity of rat glandular kallikreins. Proud, D., Bailey, G.S., Nustad, K., Gautvik, K.M. Biochem. J. (1977) [Pubmed]
  28. Kallikrein gene expression in the rat anterior pituitary. Fuller, P.J., Clements, J.A., Whitfeld, P.L., Funder, J.W. Mol. Cell. Endocrinol. (1985) [Pubmed]
  29. Immunohistochemical demonstration of tissue kallikrein in the neurons of rat brain. Kizuki, K., Suzuki, T., Kudo, M., Noguchi, T. Brain Res. (1994) [Pubmed]
  30. Kallikrein content of rat pancreatic acinar cells or islets by direct radioimmunoassay. Chao, J., Sostek, M., Shimamoto, K., Bank, H.L., Bigelow, J., Margolius, H.S. Hoppe-Seyler's Z. Physiol. Chem. (1980) [Pubmed]
  31. Influences of secretory activities in rat submandibular glands on tissue kallikrein circulating in the blood. Garrett, J.R., Chao, J., Proctor, G.B., Wang, C., Zhang, X.S., Chan, K.M., Shori, D.K. Exp. Physiol. (1995) [Pubmed]
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