Disease relevance of Klk1

• Kallikrein gene delivery improved cardiac function and reduced heart weight/body weight ratio and cardiomyocyte size without affecting mean arterial pressure 28 days after AC [1].
• RESULTS: Intramyocardial delivery of adenovirus containing the human tissue kallikrein gene resulted in expression of recombinant kallikrein in rat myocardium [1].
• Kallikrein has pleiotropic effects in inhibiting apoptosis, inflammation, proliferation, hypertrophy and fibrosis, and promoting angiogenesis and neurogenesis in different experimental animal models [2].
• Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells [3].
• These investigations indicate a pathway for thrombosis risk reduction via the plasma kallikrein/kinin and renin angiotensin systems [4].

High impact information on Klk1

• The betaNGF dimer was one of three subunits in 7S NGF; the other two were the gamma subunit, an arginine esteropeptidase or kallikrein, and the alpha subunit, an inactive kallikrein [5].
• The 9.5-kilobase nucleotide sequence of a mouse genomic clone contains one complete kallikrein gene (mGK-1), which is expressed in the male mouse submaxillary gland, and the 3' end of another (mGK-2) [6].
• A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation [7].
• The expression of many mouse kallikrein genes in the salivary gland is sexually dimorphic and inducible in females by administration of testosterone or thyroxine [8].
• A highly significant correlation between renal expression of the angiotensin type 1a receptor and kallikrein, independent of Agt genotype, is present in females (P < 0.0001) but not males (P = 0.4) [9].

Chemical compound and disease context of Klk1

• Our results demonstrate that short periods of ischemia followed by reperfusion did not cause significant alterations in kallikrein activity, Evans Blue (EB) extravasation, prokallikreins, myeloperoxidase activity or plasma creatinine concentration [10].
• Kallikrein exerted suppressive influence both on the primary and on the secondary humoral immune response accompanied by well-expressed splenomegaly but bradykinin stimulated the humoral immune response [11].
• FOY-305 (Foypan), a remedy for tumor pancreatitis, is a broad spectrum synthetic serine protease inhibitor which inhibits enzymatic activities including trypsin, thrombin, kallikrein and plasmin [12].

Biological context of Klk1

• Southern blotting and interspecific backcross analyses indicate that this murine locus represents a single copy sequence mapping to a novel locus 2.1 centimorgans from the Klk1 locus, in a region of homology between mouse chromosome 7 and the human FUT1 locus on the long arm of chromosome 19 [13].
• Differential expression phenotypes were found between the renal kallikrein gene and other members of the kallikrein gene family [14].
• Partial sequence analysis of the kallikrein genes has facilitated identification of those members of the family for which protein sequence data exist and assignment of those which are pseudogenes or encode proteins of unknown function [15].
• We have cloned a type of cDNA for a functional glandular kallikrein, designated as mouse Klk21 (mKlk21), from the adult mouse testis cDNA library. mKlk21 was expressed in the kidney, submaxillary glands, and testis of the mouse [16].
• SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner [17].

Anatomical context of Klk1

• In contrast, in the uterus or decidua, there was no expression of Klk1 until Day 7.5, when mRNA transcripts were abundant; transcripts then decreased in the Day 9.5 and Day 11 uterus [18].
• Kallikrein transcripts in the mouse lactating mammary gland were detected by primer-directed enzyme amplification of complementary DNA (cDNA) [19].
• Enhancement of lymphocyte proliferation by mouse glandular kallikrein [20].
• This cell line, which is capable of processing other prohormones, only partially processed the proform of kallikrein to its active form, secreting it predominantly as the proform [21].
• The results of immunohistochemistry and an autonomic therapy experiment showed that IL-1beta and kallikrein mK13 were co-localized in the secretory granules of granular convoluted tubular cells [22].

Associations of Klk1 with chemical compounds

• Kallikrein treatment increased cardiac nitric oxide (NO) levels and reduced NAD(P)H oxidase activity and superoxide production [1].
• Differential binding of thyroid hormone receptors to mouse glandular kallikrein gene promoters: evidence for multiple binding regions in the mGK-6 gene [23].
• Amino-terminal sequence analysis has also revealed a marked degree of homology to mouse gamma-nerve growth factor (NGF) and the kallikrein family of serine proteases [24].
• Decreased levels of kallikrein thus formed may be responsible for the inhibition of HK-dependent clotting activity and the decrease in rate and extent of HK cleavage in normal plasma on contact activation with dextran sulfate [25].
• The inhibitor also liberated kinin upon treatment with trypsin or mouse glandular kallikrein, indicating that the inhibitor is a kininogen, and the kinin liberated upon trypsinization was identified as bradykinin [26].

Physical interactions of Klk1

• These findings suggest that the alpha-NGF backbone can be corrected to a functional enzyme by the addition of a normal N-terminal structure and two catalytic site substitutions and that the 7S complex requires one kallikrein subunit in the zymogen form and one in an active conformation [27].
• Three highly specific trypsin-like proteases from mouse submaxillary gland; nerve growth factor gamma subunit, beta nerve growth factor-endopeptidase, and epidermal growth factor-binding protein were tested for kallikrein activity [28].
• The dysplasia-homing peptide is identical to a loop in kallikrein-9 and may bind a kallikrein inhibitor or substrate [29].

Enzymatic interactions of Klk1

• Therefore, kallikrein mK13 would appear to hydrolyze pro-IL-1beta between its Leu113 and Leu114 residues [22].

Regulatory relationships of Klk1

• The effects of the tetra benzamidine serine-proteinase inhibitor 1,3-di-(p-amidinophenoxy) -2,2- bis- (p-amidinophenoxymethyl)propane (TAPP-H) and related compounds, including halo-derivatives, were determined on the erythroid differentiation of murine erythroleukemic cells induced by trypsin and kallikrein [30].

Other interactions of Klk1

• Detection of a kallikrein in the mouse lactating mammary gland: a possible processing enzyme for the epidermal growth factor precursor [19].
• beta-NGF-endopeptidase: structure and activity of a kallikrein encoded by the gene mGK-22 [31].
• Sequence of the mouse glandular kallikrein gene, mGK-5 [32].
• Sequence of mGK-11, a mouse glandular kallikrein gene [33].
• These data have suggested that, like gamma-NGF and EGF-BP, beta-NGF-endopeptidase is a mouse glandular kallikrein [31].

Analytical, diagnostic and therapeutic context of Klk1

• Sequence analysis of the product over three nonconserved regions identified mGK-6 (mouse renal kallikrein) as the primary kallikrein in BALB/c mouse lactating mammary gland [19].
• In situ hybridization histochemistry shows that all kallikrein genes analyzed exhibit uniform cellular distribution of expression in the SD cells of the female [8].
• We have characterized 24 kallikrein genes by genomic cloning and restriction mapping of 310 kilobase pairs of BALB/c mouse DNA [15].
• We used a reporter assay in cell culture to functionally verify the AREs for the kallikrein 27 gene [34].
• The binding of monoclonal or polyclonal antibodies to 125I-human urinary kallikrein was not affected by human plasma kallikrein, thrombin, or urokinase in a competitive radioimmunoassay [35].

References