Source:http://linkedlifedata.com/resource/pubmed/id/11735417
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
50
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pubmed:dateCreated |
2001-12-12
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pubmed:abstractText |
hK4 (prostase, KLK4), a recently cloned prostate-specific serine protease and a member of the tissue kallikrein family, is a zymogen composed of 228 amino acid residues including an amino-terminal propiece, Ser-Cys-Ser-Gln-. A chimeric form of hK4 (ch-hK4) was constructed in which the propiece of hK4 was replaced by that of prostate-specific antigen (PSA) to create an activation site susceptible to trypsin-type proteases. ch-hK4 was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified with an overall yield of 25%. The zymogen was readily self-activated during the refolding process to generate an active form (21 kDa) of hK4 (rhK4). rhK4 cleaved the chromogenic substrates Val-Leu-Arg-pNA (S-2266), Pro-Phe-Arg-pNA (S-2302), Ile-Glu-Gly-Arg-pNA (S-2222), and Val-Leu-Lys-pNA (S-2251), indicating that rhK4 has a trypsin-type substrate specificity. The rhK4 was inhibited by aprotinin (6 kDa), forming an equimolar 27 kDa complex. rhK4 readily activated both the precursor of PSA (pro-PSA) and single chain urokinase-type plasminogen activator (scuPA, pro-uPA). rhK4 also completely degraded prostatic acid phosphatase but failed to cleave serum albumin, another protein purified from human seminal plasma. These results indicate that hK4 may have a role in the physiologic processing of seminal plasma proteins such as pro-PSA, as well as in the pathogenesis of prostate cancer through its activation of pro-uPA.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Kallikreins,
http://linkedlifedata.com/resource/pubmed/chemical/Prostate-Specific Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Seminal Plasma Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/kallikrein 4,
http://linkedlifedata.com/resource/pubmed/chemical/prostatic acid phosphatase
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15341-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11735417-Amino Acid Sequence,
pubmed-meshheading:11735417-Binding Sites,
pubmed-meshheading:11735417-Humans,
pubmed-meshheading:11735417-Hydrogen-Ion Concentration,
pubmed-meshheading:11735417-Kallikreins,
pubmed-meshheading:11735417-Male,
pubmed-meshheading:11735417-Prostate,
pubmed-meshheading:11735417-Prostate-Specific Antigen,
pubmed-meshheading:11735417-Prostatic Neoplasms,
pubmed-meshheading:11735417-Protein Precursors,
pubmed-meshheading:11735417-Protein Tyrosine Phosphatases,
pubmed-meshheading:11735417-Recombinant Proteins,
pubmed-meshheading:11735417-Seminal Plasma Proteins,
pubmed-meshheading:11735417-Serine Endopeptidases,
pubmed-meshheading:11735417-Substrate Specificity,
pubmed-meshheading:11735417-Urokinase-Type Plasminogen Activator
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pubmed:year |
2001
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pubmed:articleTitle |
Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase.
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pubmed:affiliation |
Departments of Biochemistry and Urology, University of Washington, Box 357350, Seattle, Washington 98195-7350, USA. tomt@u.washington.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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