Disease relevance of Kng1

• High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease [1].
• Role of kinins in the cardioprotective effect of preconditioning: study of myocardial ischemia/reperfusion injury in B2 kinin receptor knockout mice and kininogen-deficient rats [2].
• The objectives of the present study were to define the effects of pressure-overload cardiac hypertrophy on cardiac levels of kininogen, kallikrein and bradykinin B2 receptor mRNAs [3].
• The enzyme formed kinins at an optimal pH of 4.0 from Murphy-Sturm lymphosarcoma tissue and rat plasma kininogen substrate [4].
• Monoclonal antibody to rat plasma kininogen, obtained after immunization of mice with the kininogen prepared by conventional methods, was purified from ascites fluid and coupled to CNBr-activated Sepharose-4B [5].

High impact information on Kng1

• The protein of 448 amino acids contains a glycine/alanine-rich amino terminal region, a histidine-rich sequence with homology to a region of kininogen associated with clotting, a POU domain and a short proline/histidine-rich carboxy terminal region [6].
• By contrast, in kininogen-deficient Brown Norway Katholiek rats (BN-Ka rats), which cannot generate intrinsic bradykinin (BK), the weights of the tumors and the extent of angiogenesis were significantly less than those in BN-Ki rats [7].
• 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 [8].
• Hydroxyproline, which was recently identified in the bradykinin sequence of kininogen from the ascitic fluid of a cancer patient, was not found in the kinin moiety of this mouse kininogen [9].
• Low molecular weight kininogen was purified from mouse plasma and used as substrate for the three enzymes, and the kinin released by the enzymes was assayed by its ability to induce contraction of isolated rat uterus [10].

Biological context of Kng1

• We isolated cDNAs encoding low-molecular-weight (L-) and high-molecular-weight (H-) prekininogens from a mouse liver cDNA library using rat T-kininogen cDNA and rat H-kininogen cDNA respectively, as probes [11].
• Its amino-terminal amino acid sequence was very similar to the internal sequence of bovine high molecular weight (HMW) kininogen, which comprises fragment 1 [12].
• The DNA sequence of the region encoding bradykinin was determined for two different mouse kininogen cDNA clones, both encode the sequence Arg-BK [13].
• In blood coagulation, HMW kininogen is considered to be cleaved by a specific enzyme kallikrein [12].
• The toxin released bradykinin upon hydrolysis of kininogen [14].

Anatomical context of Kng1

• Kininogen was localized in the vascular endothelium and the smooth muscle layer [15].
• In the study presented here, we investigated the localizations of mK1, kininogen and bradykinin B2 receptors (B2Rs) in ischemic and non-ischemic left ventricles by immunohistochemistry [15].
• These results demonstrated that fibroblasts are a source of kininogen in the mouse, and that it is regulated by the inflammatory mediators, prostaglandin E2 and tumor necrosis factor [16].
• Expression of low-molecular-weight kininogen in mouse vascular smooth muscle cells [17].
• Five hybridomas were developed that produced monoclonal antibodies against plasma kininogen [18].

Associations of Kng1 with chemical compounds

• FXII(-/-) mice were then used to assess the in vivo importance of the plasma FXII/prekallikrein/kininogen pathway in provision of resting plasma bradykinin (BK) levels and in generation of plasma BK stimulated by contact with an artificial surface, using a new and greatly improved plasma BK assay developed during these studies [19].
• Atlantic salmon (Salmo salar L.) skin contains a novel kininogen and another cysteine proteinase inhibitor [20].
• Both of the enzymes, were inhibited by p-chloromercuribenzoate, N-ethylmaleimide, and high-molecular-weight kininogen, but not or only slightly inhibited by diisopropylphosphorofluoridate, antipain, leupeptin, E-64, calpain inhibitor, and phosphoramidon [21].
• Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin [22].
• Fibroblasts prepared from the meninges of newborn mice or from mouse embryos, as well as fibroblast L929 cells, secreted an immunoreactive material (ir-kininogen) against rabbit anti-mouse low-molecular-weight kininogen antibody in response to dibutyryl cAMP [16].

Physical interactions of Kng1

• The enzyme responsible, beta-NGF-endopeptidase, is structurally and functionally similar to gamma-NGF and epidermal growth factor-binding protein (EGF-BP) and cleaves mouse low molecular weight kininogen to produce bradykinin-like activity [23].

Enzymatic interactions of Kng1

• Kallikrein cleaves low molecular weight kininogen to generate vasoactive kinins, which bind to the kinin B2 receptor, triggering a host of biological effects [24].

Other interactions of Kng1

• One set (K1) is from the previously reported mouse kininogen gene [25].
• These studies further supported the view that beta-NGF-endopeptidase acts on both NGF and kininogen [23].
• Immunoblotting studies using the enhanced chemiluminescence technique indicated no crossreactivity with monoclonal antibodies to stefin B and cystatin C or with a polyclonal antibody to low M(r) kininogen [26].
• 7. The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats [22].
• Antibodies raised against E 8 reacted with stefin but not with kininogen or cystatin [27].

Analytical, diagnostic and therapeutic context of Kng1

• Northern blotting or reverse transcription-polymerase chain reaction followed by Southern blotting using mouse L- and H-kininogen cDNAs demonstrated that both L- and H-kininogens are predominantly expressed in the liver and kidney [11].
• We isolated PCR, RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE-PCR)-, and RT-PCR-generated clones from mouse kininogen family transcripts [25].
• The specificity of the monoclonal antibodies was confirmed by the immunoprecipitation of kininogen with the antibodies coupled to Sepharose-4B followed by SDS-polyacrylamide gel electrophoresis [18].
• Western blots using a bradykinin-directed monoclonal, as well as a polyclonal anti-mouse low-molecular-weight kininogen antibody, showed that ir-kininogen had a molecular weight of 80,000 and that it contained a kinin moiety [16].
• In contrast, levels of both low-molecular-weight kininogen and tissue kallikrein mRNAs were increased 7, 14 and 28 d after aortic constriction [3].

References