| Title | Activation profiles and regulatory cascades of the human kallikrein-related peptidases. | | Author(s) | Yoon H, Laxmikanthan G, Lee J, Blaber SI, Rodriguez A, Kogot JM, Scarisbrick IA, Blaber M | | Institution | Biomedical Sciences, Florida State University, Tallahassee, Fl 32306-4300. | | Source | J Biol Chem 2007 Sep 6. | | Abstract | The human kallikrein-related peptidases (KLK's) are the largest family of serine peptidases, comprising fifteen members (KLK1-15), and with the majority (KLK4-15) being identified only within the last decade. Members of this family are associated with important diseased states (including cancer, inflammation, and neurodegeneration) and have been utilized or proposed as clinically important biomarkers or therapeutic targets of interest. All human KLK's are synthesized as pre pro-forms that are proteolytically processed to secreted pro-forms via the removal of an amino-terminal secretion signal peptide. The secreted inactive pro-KLK's are then activated extracellularly to mature peptidases by specific proteolytic release of their amino-terminal pro-peptide. Although a key step in the regulation of KLK function, details regarding the activation of the human pro-KLK's (i.e. the KLK "activome") are, to a significant extent, unknown but have been postulated to involve "activation cascades" with other KLK's and endopeptidases. To characterize more completely the KLK activome we have expressed from E. coli individual KLK pro peptides fused to the amino-terminus of a soluble carrier protein. The ability of 12 different mature KLK's to process the 15 different pro-KLK peptide sequences has been determined. Various autolytic, and cross-activation relationships identified using this system have subsequently been characterized using recombinant pro-KLK proteins. The results demonstrate the potential for extensive KLK activation cascades, and when combined with available data for the tissue-specific expression of the KLK family, permit the construction of specific regulatory cascades. One such tissue-specific cascade is proposed for the CNS. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17823117 |
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