Disease relevance of KLK4

• In addition, variant-specific RT-PCRs for the cloned KLK3 and KLK4 variants as well as for the "classical" forms of the six genes were used to determine their expression profiles in healthy tissues, their regulation by steroids, and their differential expression in prostate cancer [1].
• Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells [2].
• Significant correlations were identified among mRNA of KLK4, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15 in cancer cells isolated from ascites fluid [3].
• Erythrocyte kallikrein-like esterase activity was greater in women without hypertension than in men without hypertension (p less than 0.05 to 0.001) when receiving the 9 and 109 mEq sodium diets, but values were similar in all groups receiving the 259 mEq sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Kallikrein-like esteroprotease activity and kininase activity in submandibular gland from a mutant mouse with human cystic fibrosis like alterations [5].
• Consistent with these data, small interfering RNA-mediated knockdown of endogenous KLK4 in LNCaP prostate cancer cells inhibits cell growth [6].
• Immunohistochemical analysis indicated the co-expression of agonist and PAR-2 in primary prostate cancer and bone metastases, suggesting that KLK4 signaling via this receptor will have pathological relevance [7].

Psychiatry related information on KLK4

• Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with Alzheimer's disease [8].

High impact information on KLK4

• Both MBP and poly-L-lysine induced a three- and eightfold increase in levels of kallikrein-like activity and i-kinins, respectively [9].
• Both the gel-bound fibronectin and semenogelin are progressively fragmented and solubilized by the abundant prostatic kallikrein-like protease (prostate-specific antigen) during and after seminal gel liquefaction [10].
• A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein [11].
• These data suggest that kallikrein-like activity can be generated from human basophils as a direct result of a primary IgE-mediated immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma and(or) tissue kinin-generating systems [12].
• Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions [13].

Chemical compound and disease context of KLK4

• The prostate-specific antigen-related serine protease gene, kallikrein 4 (KLK4), is expressed in the prostate and, more importantly, overexpressed in prostate cancer [14].
• Furthermore, KLK4 expression is regulated by multiple hormones in prostate cancer cells and is deregulated in the androgen-independent phase of prostate cancer [15].
• Kallikrein 4 (KLK4), a new member of the human kallikrein gene family is up-regulated by estrogen and progesterone in the human endometrial cancer cell line, KLE [16].
• 1. A kallikrein-like enzyme in plasma of patients with acute pancreatitis was further purified by successive hydroxyapatite/cellulose and Sepharose-4B column chromatography [17].
• The concentration of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), kallikrein-like enzymes and beta-glucuronidase were quantified in the cerebrospinal fluid (CSF) during spontaneous migraine attacks [18].

Biological context of KLK4

• Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4 [19].
• Given that introns <100 bp in length are retained in 95% of human genes and that splice variants of KLK3 and KLK4 retain intron III, we hypothesized that other proteins in this family, with a small intron III, may also retain it [1].
• In this study, we sought to characterize the substrate specificity of KLK4 in order to gain insight into potential physiological roles of the enzyme [20].
• Recombinant KLK4 was able to activate pro-PSA/KLK3 and degrade members of the insulin-like growth factor (IGF) binding protein (IGFBP) family [20].
• KLK4 endometrial mRNA expression was greatest on days 0, 5, and 10 when compared with days 12, 15, and 17 of the estrous cycle and greater in cyclic compared with pregnant gilts [21].

Anatomical context of KLK4

• CD4 T cell clones specific for these epitopes are shown to efficiently and specifically recognize both recombinant KLK4 protein and lysates from prostate tumor cell lines virally infected to express KLK4 [22].
• BACKGROUND: Prostase/KLK4 is a member of the human kallikrein (KLK) gene family that is expressed in prostate epithelial cells under the regulation of androgenic hormones [20].
• A brief review of dental enamel formation is presented, followed by a more detailed analysis of enamelysin and KLK4 expression, structure, and function [23].
• Expression of KLK4 was more intense in the stroma and uterine epithelium from days 0 to 10 of the estrous cycle [21].
• Prostase shares 35% amino acid identity with prostate-specific antigen (PSA) and 78% identity with the porcine enamel matrix serine proteinase 1, an enzyme involved in enamel matrix degradation and with a putative role in the disruption of intercellular junctions [24].

Associations of KLK4 with chemical compounds

• Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression [24].
• These cell lines now provide a model system to study the role of KLK4 and the molecular mechanisms of KLK4 regulation by estrogen and progesterone, in endometrial tumorigenesis [16].
• Ovarian tissues were then classified as KLK4-positive or -negative, based on ethidium bromide visualization of the PCR product on agarose gels [25].
• Studies suggest that the actions of insulin on glucose metabolism may be mediated through activation of a membrane-bound serine protease with properties similar to a kallikrein-like enzyme [26].
• These studies describe the IgE-mediated relase of a basophil kallikrein-like enzyme that is an arginine esterase and is inhibited by plasma, diisopropylphosphofluoridate, and Trasylol [12].

Physical interactions of KLK4

• The kallikrein-like activity in malignant ascites was found in complex with alpha 2-macroglobulin [27].

Enzymatic interactions of KLK4

• 8. 4. A kallikrein-like enzyme is able to cleave a kininogen analog to release bradykinin, and the B beta chain of fibrinogen [28].

Other interactions of KLK4

• For KLK4, KLK8, and KLK13 mRNA, splice variants were identified to be their major mRNA species [29].
• Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25-44%) and do not contain a conventional kallikrein loop [30].
• Using this methodology, three naturally processed CD4 epitopes derived from the KLK4 sequence are identified [22].
• KLK4 concentrates at the enamel surface when the enamel matrix disappears, and aggressively degrades amelogenin in vitro [23].
• The prostase cDNA encodes a putative 254-aa polypeptide with a conserved serine protease catalytic triad and an amino-terminal pre-propeptide sequence, indicating a potential secretory function [24].

Analytical, diagnostic and therapeutic context of KLK4

• Finally, in situ hybridization on normal and hyperplastic prostate samples in tissue microarrays indicate that KLK4 is predominantly expressed in the basal cells of the normal prostate gland and overexpressed in prostate cancer [31].
• In addition to detailed mapping of the KLK4 mRNA 5' end by RT-PCR, this conclusion is supported by predominantly nuclear localization of the hK4 protein in the cell, documented by both immunofluorescence and cell fractionation experiments [31].
• Tissue kallikrein levels in serum and urine and levels of the erythrocyte kallikrein-like enzyme were measured with specific radioimmunoassays or with an activity assay, respectively [4].
• In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples [32].
• This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments [32].

References