Τίτλος:
Emerging Interest in the Kallikrein Gene Family for Understanding and Diagnosing Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Kallikreins are proteolytic enzymes that constitute a subfamily of serine proteases. Novel kallikrein genes were cloned recently, and it was shown that the human kallikrein family contains 15 genes tandemly aligned on chromosomal locus 19q13.3-q13.4. Based on their altered expression in tumor cells, kallikreins may be involved in the pathogenesis and/or progression of cancer. Evidence is presented that certain kallikreins may be exploited as diagnostic cancer biomarkers. Although the function(s) of novel kallikreins is currently unknown, increasing evidence suggests that kallikreins may participate in regulatory enzymatic cascade(s). Elucidation of the function of novel kallikreins largely depends on the availability of active recombinant proteins. Here, the zymogen for kallikrein 13 was overexpressed in Pichia pastoris and biochemically characterized. It was shown that the kallikrein 13 zymogen displays intrinsic catalytic activity leading to autoactivation. A clipped form of kallikrein 13 was identified, indicating autocatalytic cleavage at the internal bond R114-S115. Mature kallikrein 13 displays trypsin-like activity with restricted specificity on synthetic and protein substrates. Combinatorial P1-Lys libraries of tetrapeptide fluorogenic substrates were synthesized and used for the profiling of the P2 specificity of selected kallikreins. Interestingly, it was shown that human kallikrein 13, similarly to PSA, could specifically cleave human plasminogen to generate angiostatin-like fragments, suggesting that specific kallikreins may have antiangiogenic actions. An understanding of the physiology of human kallikreins is emerging with potential clinical applications.
Συγγραφείς:
Sotiropoulou, G.
Rogakos, V.
Tsetsenis, T.
Pampalakis, G.
Zafiropoulos, N.
Simillides, G.
Yiotakis, A.
Diamandis, E.P.
Περιοδικό:
Oncology Research
Εκδότης:
Cognizant Communication Corporation
Λέξεις-κλειδιά:
angiogenesis inhibitor; angiostatin; enzyme precursor; kallikrein; kallikrein 13; lysine; plasminogen; recombinant protein; serine proteinase; unclassified drug; KLK13 protein, human; KLK15 protein, human; KLK6 protein, human; plasminogen; recombinant protein; tumor marker, cancer diagnosis; chromosome 19q; combinatorial chemistry; conference paper; disease course; disease marker; enzyme regulation; evidence based medicine; gene expression regulation; gene locus; genetic analysis; human; human cell; molecular cloning; pathogenesis; Pichia pastoris; priority journal; protein degradation; protein family; amino acid sequence; article; comparative study; enzyme specificity; enzymology; genetics; glycosylation; isolation and purification; kinetics; metabolism; neoplasm; physiology, Amino Acid Sequence; Cloning, Molecular; Glycosylation; Humans; Kallikreins; Kinetics; Neoplasms; Plasminogen; Recombinant Proteins; Substrate Specificity; Tumor Markers, Biological
DOI:
10.3727/096504003108748393
