An overview of the kallikrein gene families in humans and other species: emerging candidate tumour markers

Yousef, George M.; Diamandis, Eleftherios P.

doi:10.1016/s0009-9120(03)00055-9

Cited by 88 publications

(78 citation statements)

References 102 publications

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“…High levels of proteolytic activities have been implicated in neoplastic progression (11,29). Serine proteases have been implicated in the degradation of ECM in various types of cancers and have been proposed as potential diagnostic and therapeutic targets for human tumors (5,6,30). It is known that two members of the serine protease family, prostate-specific antigen and human kallikrein 2, serve as important prostate carcinoma biomarkers (6,31).…”

Section: Discussionmentioning

confidence: 99%

“…An array of ECM-degrading proteases have been identified and implicated in cancer invasion and metastasis (5). The serine proteases with conserved residues of histidine, aspartate, and serine constitute a novel family of transmembrane enzymes involved in numerous biological processes, including activation of growth and angiogenic factors, and in the degradation of ECM components (6). The high expression of serine and other proteases in CaP are reported to be correlated with poor survival of the patients (7,8).…”

Section: Introductionmentioning

confidence: 99%

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A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1

Saleem¹,

Adhami²,

Zhong³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

131

101

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Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix, and in the progression of some epithelial cancers. Here, we establish the clinical significance of matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), during the progression of human prostate cancer (CaP). Methods: The expression patterns of matriptase and HAI-1 were determined in primary cultures of normal human prostate epithelial (NHPE) cells, human CaP cells LNCaP, DU-145, CWR22RN1, and PC-3, and in tissue samples of 172 patients with normal prostate, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma of different tumor grades. Results: The protein and mRNA levels of matriptase were significantly higher in all carcinoma cells as compared

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1

Saleem¹,

Adhami²,

Zhong³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

131

101

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“…1) with amino acid sequence identity of about 80% for the classical and 40% among the new tissue kallikreins, respectively (8,9). According to phylogenetic analyses, hK1, hK2, and hK3 form a subgroup of particularly closely related proteinases, whereas the tissue kallikreins hK4-hK15 diverge into several subgroups, namely hK4/hK5/hK7, hK6/ hK13/hK14, hK8/hK10/hK12, and hK9/hK11/hK15 (2,10). In Table 1, the 15 human tissue kallikreins are listed together with their synonyms, their primary tissue localization, and their data base accession numbers (11).…”

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confidence: 99%

Specificity Profiling of Seven Human Tissue Kallikreins Reveals Individual Subsite Preferences

Debela

Magdolen

Schechter

et al. 2006

Journal of Biological Chemistry

133

121

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Human tissue kallikreins (hKs) form a family of 15 closely related (chymo)trypsin-like serine proteinases. These tissue kallikreins are expressed in a wide range of tissues including the central nervous system, the salivary gland, and endocrine-regulated tissues, such as prostate, breast, or testis, and may have diverse physiological functions. For several tissue kallikreins, a clear correlation has been established between expression and different types of cancer. For example, the prostate-specific antigen (PSA or hK3) serves as tumor marker and is used to monitor therapy response. Using a novel strategy, we have cloned, expressed in Escherichia coli or in insect cells, refolded, activated, and purified the seven human tissue kallikreins hK3/PSA, hK4, hK5, hK6, hK7, hK10, and hK11. Moreover, we have determined their extended substrate specificity for the nonprime side using a positional scanning combinatorial library of tetrapeptide substrates. hK3/PSA and hK7 exhibited a chymotrypsin-like specificity preferring large hydrophobic or polar residues at the P1 position. In contrast, hK4, hK5, and less stringent hK6 displayed a trypsin-like specificity with strong preference for P1-Arg, whereas hK10 and hK11 showed an ambivalent specificity, accepting both basic and large aliphatic P1 residues. The extended substrate specificity profiles are in good agreement with known substrate cleavage sites but also in accord with experimentally solved (hK4, hK6, and hK7) or modeled structures. The specificity profiles may lead to a better understanding of human tissue kallikrein functions and assist in identifying their physiological protein substrates as well as in designing more selective inhibitors.The tissue kallikreins constitute a subgroup of the chymotrypsin-like serine proteinase family S1A of clan PA(S) (1). They are highly homologous to the "true tissue kallikrein" K1, which is encoded in mammals, for example, by the human KLK1 or the mouse Klk1 genes (2). The 15 human KLK genes code for the classical tissue kallikreins hK1, hK2, and the prostate-specific antigen (PSA, 5 hK3) as well as for the 12 more recently discovered so-called new tissue kallikreins, hK4 to hK15, named in chronological order of their characterization (3-7). These genes share common characteristics such as a similar exon/intron organization and encode single-chain pre-proproteinases, which consist of a signal peptide, a generally short, 4 -9-residue-long pro-peptide (only hK5 harbors a rather long propeptide of 37 residues), and a chymotrypsin-or trypsin-like catalytic domain ( Fig. 1) with amino acid sequence identity of about 80% for the classical and 40% among the new tissue kallikreins, respectively (8, 9). According to phylogenetic analyses, hK1, hK2, and hK3 form a subgroup of particularly closely related proteinases, whereas the tissue kallikreins hK4-hK15 diverge into several subgroups, namely hK4/hK5/hK7, hK6/ hK13/hK14, hK8/hK10/hK12, and hK9/hK11/hK15 (2, 10). In Table 1, the 15 human tissue kallikreins are listed together with their s...

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“…Furthermore, these proteases contribute These authors contributed equally to this work. a to many diseases and are particularly involved in multiple organ failure due to sepsis and trauma (Jochum et al, 1994;Waydhas et al, 1996), as well as tumor progression (Johnsen et al, 1998;Foekens et al, 2003;Reuning et al, 2003;Yousef and Diamandis, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Structural features and specific expression patterns of testisin suggest that it regulates proteolytic events associated with testicular germ cell development (Hooper et al, 1999(Hooper et al, , 2000. Further serine proteases which seem to play a (patho)physiological role, especially in the male genital tract or in cancer progression, belong to the human kallikrein-related peptidases (Lundwall et al, 2006;Paliouras and Diamandis, 2006;Whitbread et al, 2006;Lundwall and Brattsand, 2008), encoded by the kallikrein gene locus which comprises 15 serine protease genes (Yousef et al, 2000;Clements et al, 2001) with prostate-specific antigen (KLK3) as one of the best known representatives (Yousef and Diamandis, 2003;Lilja et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

T-SP1: a novel serine protease-like protein predominantly expressed in testis

Neth

Profanter²,

Geißler³

et al. 2008

BCHM

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An overview of the kallikrein gene families in humans and other species: emerging candidate tumour markers

Cited by 88 publications

References 102 publications

A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1

A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1

Specificity Profiling of Seven Human Tissue Kallikreins Reveals Individual Subsite Preferences

T-SP1: a novel serine protease-like protein predominantly expressed in testis

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