The New Kallikrein-like Gene, KLK-L2

Yousef, George M.; Diamandis, Eleftherios P.

doi:10.1074/jbc.274.53.37511

Cited by 83 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the semenogelins are co localized with PSA, KLK2 and KLK5 in several tissues outside the reproductive organs, such as breast,salivary gland, trachea and the intestine [26,[33][34][35] The two semenogelin genes are surrounded by a locus containing 14 genes that are structurally similar in that they exhibit conservation of the first exon encoding the signal peptide and the last exon containing the 3' untranslated nucleotides. The locus produces small proteins that have been suggested to inhibit serine proteases and that have been found to contain a characteristic structural motif, which was first discovered in whey acidic protein and is now known to consist of four conserved disulfide bridges.…”

mentioning

confidence: 99%

The semenogelins: proteins with functions beyond reproduction?

Jonsson

Lundwall

Malm

2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

The semenogelins: proteins with functions beyond reproduction?

Jonsson

Lundwall

Malm

2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…The large size of the kallikrein gene family in other species, such as rat and mouse, where kallikreins are encoded by [13][14][15][16][17][18][19][20][21][22][23][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).…”

mentioning

confidence: 99%

“…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 (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.…”

mentioning

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…The human kallikrein gene 5 (KLK5), initially known as kallikrein-like gene 2 (KLK-L2) or human stratum corneum tryptic enzyme (HSCTE), is a newly identified member of the family [9,10]. Kallikrein-related peptidase 5 (KLK5) encoded by KLK5 is a serine protease, under the transcriptional control of estrogens and progestins.…”

Section: Introductionmentioning

confidence: 99%

“…Kallikrein-related peptidase 5 (KLK5) encoded by KLK5 is a serine protease, under the transcriptional control of estrogens and progestins. KLK5 comprises 293 amino acids and is featured as a pre-pro-enzyme [9,10]. Activated KLK5 protein has trypsin-like activity, and its activation depends on the proteolytic cleavage of their N-terminus pro-peptide via autocatalysis or through other KLKs [5].…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of an ELISA method for the measurement of kallikrein-related peptidase 5 (KLK5) in human serum

Wu¹,

Liu²,

Chen³

et al. 2013

OJCD

View full text Add to dashboard Cite

Kallikrein-related peptidases (KLKs) have been proposed as potential cancer biomarkers. Kallikreinrelated peptidase 5 (KLK5) is a secreted trypsin-like protease of the KLKs. Until now, detection of KLK5 in both biological fluids and tissues has been described frequently due to the potential of being a new cancer biomarker. Our objective was to prepare KLK5 antibodies and establish an ELISA method for KLK5 to study the possible clinical application of KLK5 as a biomarker for malignancies. In this study, recombinant KLK5 protein was produced and purified using a prokaryotic expression system, and then used as immunogen to generate antibodies. High titers of specific antibodies were measured in serum of rabbits after the forth booster injection. And the titer of the antiserum reached 1:10 6 . We have also generated monoclonal antibodies using hybridoma technology and the titer reached 1:10 5 . The activity of KLK5 antibodies was characterized by Western blot and immunohistochemistry. To quantitatively examine KLK5 in serum samples, we established double antibody sandwich ELISA method using mouse mAb as capture and rabbit pAb as tracer antibody. We have detected KLK5 levels in ovarian cancer serum to ensure that our sandwich ELISA measurement to have high sensitivity and specificity. The ranges of linearity reached by the standard curves of the newly developed ELISA were 0.45 ng/mL to 125 ng/mL. The detection limit of the method, defined as the concentration of KLK5 can be distinguished, was 0.20 ng/mL. Median serum KLK5 levels were 3.77 ng/mL and 0.86 ng/mL in ovarian cancer patients and normal female, respectively (P < 0.001). In conclusion, we prepare anti-KLK5 antibodies and develop the sandwich-type ELISA assay for KLK5. Our preliminary findings prompt that KLK5 may be a new potential biomarker for the diagnosis and prognosis in patients with ovarian.

show abstract

The New Kallikrein-like Gene, KLK-L2

Cited by 83 publications

References 35 publications

The semenogelins: proteins with functions beyond reproduction?

The semenogelins: proteins with functions beyond reproduction?

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

Development and evaluation of an ELISA method for the measurement of kallikrein-related peptidase 5 (KLK5) in human serum

Contact Info

Product

Resources

About