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rdf:type |
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lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0033634,
umls-concept:C0036025,
umls-concept:C0086418,
umls-concept:C0220905,
umls-concept:C0256371,
umls-concept:C0332437,
umls-concept:C1514562,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
3
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pubmed:dateCreated |
1996-5-2
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pubmed:abstractText |
This study demonstrates that the isolated regulatory (R) domain (amino acids 1-270) of human protein kinase C alpha (PKC alpha) is a potent inhibitor of PKC beta-I activity in a yeast expression system. The PKC alpha R domain fused to glutathione-S-transferase competitively inhibited the activity of yeast-expressed rat PKC beta-I in vitro (Ki = 0.2 microns) and was 400-fold more potent than a synthetic pseudosubstrate peptide corresponding to amino acids 19-36 from PKC alpha. In contrast, the fusion protein did not affect the activity of the purified catalytic subunit of cAMP-dependent protein kinase. The PKC alpha R domain (without glutathione-S-transferase [GST]) also was tested for its ability to inhibit PKC beta-I activity in vivo, in a yeast strain expressing rat PKC beta-I. Upon treatment with a PKC-activating phorbol ester, yeast cells expressing rat PKC beta-I were growth-inhibited and a fraction of the cells appeared as long chains. Coexpression of the R domain with rat PKC beta-I blocked the phorbol ester-induced inhibition of yeast cell growth and the phorbol ester-dependent alterations in yeast cell morphology. These results indicate that the R domain of PKC alpha acts as a dominant inhibitor of PKC activity in vivo and thus provides a useful genetic tool to assess the roles of PKC in various signal transduction processes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol 12,13-Dibutyrate,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9541
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
609-17
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8600165-Amino Acid Sequence,
pubmed-meshheading:8600165-Animals,
pubmed-meshheading:8600165-Base Sequence,
pubmed-meshheading:8600165-Catalysis,
pubmed-meshheading:8600165-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:8600165-Enzyme Activation,
pubmed-meshheading:8600165-Enzyme Inhibitors,
pubmed-meshheading:8600165-Glutathione Transferase,
pubmed-meshheading:8600165-Humans,
pubmed-meshheading:8600165-Isoenzymes,
pubmed-meshheading:8600165-Molecular Sequence Data,
pubmed-meshheading:8600165-Phorbol 12,13-Dibutyrate,
pubmed-meshheading:8600165-Protein Kinase C,
pubmed-meshheading:8600165-Protein Kinase C-alpha,
pubmed-meshheading:8600165-RNA, Messenger,
pubmed-meshheading:8600165-Radioligand Assay,
pubmed-meshheading:8600165-Rats,
pubmed-meshheading:8600165-Recombinant Fusion Proteins,
pubmed-meshheading:8600165-Saccharomyces cerevisiae
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pubmed:year |
1996
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pubmed:articleTitle |
Regulatory domain of human protein kinase C alpha dominantly inhibits protein kinase C beta-I-regulated growth and morphology in Saccharomyces cerevisiae.
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pubmed:affiliation |
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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