Primary Structure of a Human Glandular Kallikrein Gene

Schedlich, Lynette J.; Bennetts, Bruce; Morris, Brian J.

doi:10.1089/dna.1987.6.429

Cited by 269 publications

(152 citation statements)

References 33 publications

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“…We were able to identify three new kallikrein-like genes; KLK-L1 (for kallikrein-like gene 1) (15) KLK-L2 (for kallikrein-like gene 2) (16,17), and KLK-L3. 2 Here, we describe the cloning of a new kallikrein-like gene, named kallikrein-like gene 4 (KLK-L4), together with its precise chromosomal localization in relation to other kallikreins and its tissue expression pattern. We further describe identification of alternatively spliced forms of this gene in some tissues.…”

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confidence: 99%

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Yousef¹,

Chang²,

Diamandis³

2000

Journal of Biological Chemistry

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Kallikreins are a subgroup of serine proteases and these proteolytic enzymes have diverse physiological functions in many tissues. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. In rodents, kallikreins constitute a large multigene family, but in humans, only three genes were identified. By using the positional candidate gene approach, we were able to identify a new kallikrein-like gene, tentatively named KLK-L4 (for kallikrein-like gene 4). This new gene maps to chromosome 19q13.3-q13.4, is formed of five coding exons and four introns, and shows structural similarity to other kallikreins and kallikrein-like genes. KLK-L4 is expressed in a variety of tissues including prostate, salivary gland, breast, and testis. Our preliminary results show that KLK-L4 is down-regulated, at the mRNA level, in breast cancer tissues and breast cancer cell lines. Its expression is regulated by steroid hormones in the breast cancer cell line BT-474. This gene may be involved in the pathogenesis and/or progression of breast cancer and may find applicability as a novel cancer biomarker.Prostate-specific antigen (PSA) 1 testing has revolutionized the management of patients with prostate cancer (1). The PSA gene (KLK3) is a member of the human tissue kallikrein gene family, which is also comprised of human glandular kallikrein 2 (KLK2) (2) and pancreatic/renal kallikrein (KLK1) (3) genes. More recently, new serine proteases with a high degree of homology to the kallikrein genes were cloned (4 -9). The successful diagnostic use of PSA in prostate cancer suggests that other related or unrelated molecules might be discovered and serve as diagnostic tests for breast, ovarian, and other cancers. In addition to PSA, human glandular kallikrein 2 (encoded by the KLK2 gene) may be useful as an adjuvant diagnostic marker for prostate cancer (10). Accumulating evidence indicates that some members of the kallikrein gene family are implicated in carcinogenesis. The normal epithelial cell-specific 1 gene (NES1) was found to be a tumor suppressor (11) that is down-regulated during breast cancer progression. The zyme/ protease M/neurosin gene is expressed in primary breast cancers but is down-regulated at metastatic sites (4).The large size of the kallikrein gene family in other species, such as rat and mouse, where kallikreins are encoded by 13-24 genes (12-13), and the recent identification of new kallikreinlike genes suggested that the human kallikrein gene family may be larger than previously thought. The rodent kallikrein genes are located in clusters on chromosome 7, and the region between two mouse kallikrein genes in a cluster can be as small as 3-7 kb (14).In our efforts to identify new kallikrein-like genes that might be useful as diagnostic and/or prognostic markers for cancer, we studied a genomic area of ϳ300 kb around chromosome 19q13.3-q13.4, where the known human kallikrein genes are localized. We were able to identify three new kallikrein-like genes; KLK-L1 (for kallikrein-like gene 1) (15) KLK-L2 (fo...

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confidence: 99%

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Yousef¹,

Chang²,

Diamandis³

2000

Journal of Biological Chemistry

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“…In this region, rapidly kinin-liberating 'true' TKs differ from TK-like enzymes from the male sexual tract in humans (as compiled in Schedlich et al, 1987) by as many as 17 or 20, in the dog (Chapdelaine et al, 1991;Gauthier et al, 1994) by 16, and in the rat (compilation in Wines et al, 1991) by 12 or 13 amino acid residues. The unusual sequence similarity cautioned against inferring the identity of a guinea pig TK preparation from results of amino-terminal sequencing alone.…”

Section: Discussionmentioning

confidence: 99%

Not More than Three Tissue Kallikreins Identified from Organs of the Guinea Pig

Fiedler¹,

Betz²,

Hinz³

et al. 1999

Biological Chemistry

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The large and varied multigene families of tissue kallikreins of rat and mouse are considered to selectively release as many bioactive peptides. In order to determine whether a similar family of enzymes is expressed in the organs of the guinea pig purification studies were performed. Tissue kallikreins from the submandibular gland, coagulating gland/prostate complex and the pancreas were separated by affinity chromatography on benzamidine-Sepharose. Amino-terminal sequences, the patterns of hydrolysis rates of a number of peptide p-nitroanilides, inactivation rates by active site-directed irreversible inhibitors, specific kininogenase activities and types of kinin released were used to probe the identity of the isolated enzymes.Guinea pig tissue kallikreins 1 and 2 have been reported previously. In the present study we have identified a third type, designated tissue kallikrein 1a because of its sequence similarity to kallikrein 1, which differs from the latter in the catalytic properties. The inferred occurrence of not more than two or three independent tissue kallikrein genes in the guinea pig contrasts with the varied family of enzymes expressed by the large number of such genes present in rats and mice. Expression in the guinea pig (and also in humans) of only a small number of tissue kallikreins makes specific processing of a multitude of biologically active peptides by such enzymes unlikely.

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“…In the genome of the mouse, the 24 kallikreinrelated genes are highly homologous and are clustered on chromosome 7 [28]. In man, the kallikrein family may be smaller with a maximum of 3 members [29], respectively. The absence of genes highly homologous to canine prostate arginine esterase in Southern blot hybridization experiments does not exclude the possibility of a larger kallikrein family in that species or that all these genes could be clustered on a single gene locus.…”

Section: Discussionmentioning

confidence: 99%

Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

et al. 1988

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The nucleotide sequence of canine prostate arginine esterase mRNA was determined using a 400 bp cDNA clone and primer-extended cDNA transcripts for the 5'coding and noncoding regions. The mRNA contains 864 nucleotides encoding a protein of 236 amino acids preceded by 24 amino acids which constitutes both the signal and the zymogen peptides. The sequence indicates the presence of one potential glycosylation site. A high degree of homology was found between the canine enzyme and other members of the kallikrein family including human prostate specific antigen. The protein appears to be specified by a single gene.

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Primary Structure of a Human Glandular Kallikrein Gene

Cited by 269 publications

References 33 publications

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Not More than Three Tissue Kallikreins Identified from Organs of the Guinea Pig

Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

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