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Endocrine Reviews 22 (2): 184-204
Copyright © 2001 by The Endocrine Society

The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease1

George M. Yousef and Eleftherios P. Diamandis

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L5

The human tissue kallikrein gene family was, until recently, thought to consist of only three genes. Two of these human kallikreins, prostate-specific antigen and human glandular kallikrein 2, are currently used as valuable biomarkers of prostatic carcinoma. More recently, new kallikrein-like genes have been discovered. It is now clear that the human tissue kallikrein gene family contains at least 15 genes. All genes share important similarities, including mapping at the same chromosomal locus (19q13.4), significant homology at both the nucleotide and protein level, and similar genomic organization. All genes encode for putative serine proteases and most of them are regulated by steroid hormones. Recent data suggest that at least a few of these kallikrein genes are connected to malignancy. In this review, we summarize the recently accumulated knowledge on the human tissue kallikrein gene family, including gene and protein structure, predicted enzymatic activities, tissue expression, hormonal regulation, and alternative splicing. We further describe the reported associations of the human kallikreins with various human diseases and identify future avenues for research.




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Detection of Human Kallikrein 4 in Healthy and Cancerous Prostatic Tissues by Immunofluorometry and Immunohistochemistry
Clin. Chem., August 1, 2002; 48(8): 1232 - 1240.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
F. X. Gomis-Ruth, A. Bayes, G. Sotiropoulou, G. Pampalakis, T. Tsetsenis, V. Villegas, F. X. Aviles, and M. Coll
The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family
J. Biol. Chem., July 19, 2002; 277(30): 27273 - 27281.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. J. Bernett, S. I. Blaber, I. A. Scarisbrick, P. Dhanarajan, S. M. Thompson, and M. Blaber
Crystal Structure and Biochemical Characterization of Human Kallikrein 6 Reveals That a Trypsin-like Kallikrein Is Expressed in the Central Nervous System
J. Biol. Chem., June 28, 2002; 277(27): 24562 - 24570.
[Abstract] [Full Text] [PDF]


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BrainHome page
I. A. Scarisbrick, S. I. Blaber, C. F. Lucchinetti, C. P. Genain, M. Blaber, and M. Rodriguez
Activity of a newly identified serine protease in CNS demyelination
Brain, June 1, 2002; 125(6): 1283 - 1296.
[Abstract] [Full Text] [PDF]


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Cancer Epidemiol. Biomarkers Prev.Home page
F. J. Meng, A. Shan, L. Jin, and C. Y. F. Young
The Expression of a Variant Prostate-specific Antigen in Human Prostate
Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 305 - 309.
[Abstract] [Full Text] [PDF]


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Biol. Reprod.Home page
M. R. Allen, B. R. Zhang, A. M. Hettinger, D. W. Goad, J. R. Malayer, and R. D. Geisert
Detection of Bradykinin and Bradykinin-{beta}2 Receptors in the Porcine Endometrium During the Estrous Cycle and Early Pregnancy
Biol Reprod, March 1, 2002; 66(3): 574 - 579.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
E. P. Diamandis, A. Okui, S. Mitsui, L.-Y. Luo, A. Soosaipillai, L. Grass, T. Nakamura, D. J. C. Howarth, and N. Yamaguchi
Human Kallikrein 11: A New Biomarker of Prostate and Ovarian Carcinoma
Cancer Res., January 1, 2002; 62(1): 295 - 300.
[Abstract] [Full Text] [PDF]


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J. Histochem. Cytochem.Home page
C. D. Petraki, V. N. Karavana, P. T. Skoufogiannis, S. P. Little, D. J.C. Howarth, G. M. Yousef, and E. P. Diamandis
The Spectrum of Human Kallikrein 6 (Zyme/Protease M/Neurosin) Expression in Human Tissues as Assessed by Immunohistochemistry
J. Histochem. Cytochem., November 1, 2001; 49(11): 1431 - 1442.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
G. M. Yousef, L. G. Kyriakopoulou, A. Scorilas, S. Fracchioli, B. Ghiringhello, M. Zarghooni, A. Chang, M. Diamandis, G. Giardina, W. J. Hartwick, et al.
Quantitative Expression of the Human Kallikrein Gene 9 (KLK9) in Ovarian Cancer: A New Independent and Favorable Prognostic Marker
Cancer Res., November 1, 2001; 61(21): 7811 - 7818.
[Abstract] [Full Text] [PDF]




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