| Autor: |
Sotiropoulou G; Department of Pharmacy, School of Health Sciences, University of Patras, Rion, 26500 Patras, Greece. G.Sotiropoulou@upatras.gr, Rogakos V, Tsetsenis T, Pampalakis G, Zafiropoulos N, Simillides G, Yiotakis A, Diamandis EP |
| Jazyk: |
angličtina |
| Zdroj: |
Oncology research [Oncol Res] 2003; Vol. 13 (6-10), pp. 381-91. |
| DOI: |
10.3727/096504003108748393 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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