Tissue kallikreins: new players in normal and abnormal cell growth?
Serine proteases are proteolytic enzymes with an active serine residue in their catalytic site. Kallikreins are a subgroup of the serine protease family and are known to have diverse physiological functions. The human tissue kallikrein gene family has now been fully characterized and includes 15 members, clustered in a 300 kb region on chromosome 19q13.4. In this review, we discuss the common structural features of kallikreins at the DNA, mRNA and protein levels. Kallikreins are secreted as inactive zymogens and are activated by cleavage of an N-terminal peptide. Some kallikreins can undergo autoactivation while others may be activated by other kallikreins or other proteases. Most kallikreins are predicted to have trypsin-like enzymatic activity except for three members which may have chymotrypsin-like activity. Circumstantial evidence suggests that at least some kallikreins may be part of an enzymatic cascade pathway which is activated in aggressive forms of ovarian and probably other cancers. Accumulating evidence suggests potential diagnostic and/or prognostic roles of kallikreins in diverse malignancies. In addition to PSA, many other kallikreins show differential expression in malignancy. For example, hK6, 10 and 11 are promising serological markers for ovarian cancer diagnosis. KLK10 may act as a tumor suppressor. In addition to their diagnostic and prognostic values, kallikreins may also be good therapeutic targets.
Yousef
George M
GM
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Diamandis
Eleftherios P
EP
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D002455:Cell Division / Q000502:physiology*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016384:Consensus Sequence; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D011487:Protein Conformation; D016415:Sequence Alignment; D017385:Sequence Homology; D020840:Tissue Kallikreins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020840:Tissue Kallikreins