Activation profiles of human kallikrein-related peptidases by proteases of the thrombostasis axis

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dc.contributor.authorYoon, Hyesook
dc.contributor.authorBlaber, Sachiko I.
dc.contributor.authorEvans, D. Michael
dc.contributor.authorTrim, Julie
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorScarisbrick, Isobel A.
dc.contributor.authorBlaber, Michael
dc.contributor.institutionFlorida State Univ
dc.contributor.institutionVantia Ltd
dc.contributor.institutionFerring Res Ltd
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMayo Med & Grad Sch
dc.date.accessioned2016-01-24T13:51:47Z
dc.date.available2016-01-24T13:51:47Z
dc.date.issued2008-11-01
dc.description.abstractThe human kallikrein-related peptidases (KLKs) comprise 15 members (KLK1-15) and are the single largest family of serine proteases. the KLKs are utilized, or proposed, as clinically important biomarkers and therapeutic targets of interest in cancer and neurodegenerative disease. All KLKs appear to be secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their N-terminal pro-peptide. This processing is a key step in the regulation of KLK function. Much recent work has been devoted to elucidating the potential for activation cascades between members of the KLK family, with physiologically relevant KLK regulatory cascades now described in skin desquamation and semen liquefaction. Despite this expanding knowledge of KLK regulation, details regarding the potential for functional intersection of KLKs with other regulatory proteases are essentially unknown. To elucidate such interaction potential, we have characterized the ability of proteases associated with thrombostasis to hydrolyze the pro-peptide sequences of the KLK family using a previously described pro-KLK fusion protein system. A subset of positive hydrolysis results were subsequently quantified with proteolytic assays using intact recombinant pro-KLK proteins. Pro-KLK6 and 14 can be activated by both plasmin and uPA, with plasmin being the best activator of pro-KLK6 identified to date. Pro-KLK11 and 12 can be activated by a broad-spectrum of thrombostasis proteases, with thrombin exhibiting a high degree of selectivity for pro-KLK12. the results show that proteases of the thrombostasis family can efficiently activate specific pro-KLKs, demonstrating the potential for important regulatory interactions between these two major protease families.en
dc.description.affiliationFlorida State Univ, Coll Med, Dept Chem & Biochem, Tallahassee, FL 32306 USA
dc.description.affiliationFlorida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA
dc.description.affiliationVantia Ltd, Southampton SO16 7NP, Hants, England
dc.description.affiliationFerring Res Ltd, Southampton SO16 7NP, Hants, England
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-0404420 São Paulo, Brazil
dc.description.affiliationMayo Med & Grad Sch, Program Mol Neurosci, Rochester, MN 55905 USA
dc.description.affiliationMayo Med & Grad Sch, Dept Neurol, Rochester, MN 55905 USA
dc.description.affiliationMayo Med & Grad Sch, Dept Phys Med & Rehabil, Rochester, MN 55905 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-0404420 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNIH
dc.description.sponsorshipNational Multiple Sclerosis Society
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDNIH: 1R15NS057771-01
dc.description.sponsorshipIDNational Multiple Sclerosis Society: PP1113
dc.description.sponsorshipIDNational Multiple Sclerosis Society: RG3367
dc.format.extent1998-2007
dc.identifierhttp://dx.doi.org/10.1110/ps.036715.108
dc.identifier.citationProtein Science. Woodbury: Cold Spring Harbor Lab Press, Publications Dept, v. 17, n. 11, p. 1998-2007, 2008.
dc.identifier.doi10.1110/ps.036715.108
dc.identifier.issn0961-8368
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30981
dc.identifier.wosWOS:000260423400013
dc.language.isoeng
dc.publisherCold Spring Harbor Lab Press, Publications Dept
dc.relation.ispartofProtein Science
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectkallikrein-related peptidasesen
dc.subjectKLKen
dc.subjectactivation cascadeen
dc.subjectthrombostasisen
dc.subjectplasminen
dc.subjectthrombinen
dc.subjectinflammationen
dc.titleActivation profiles of human kallikrein-related peptidases by proteases of the thrombostasis axisen
dc.typeinfo:eu-repo/semantics/article
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