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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0017638,
umls-concept:C0028778,
umls-concept:C0030685,
umls-concept:C0033634,
umls-concept:C0044369,
umls-concept:C0070750,
umls-concept:C0084393,
umls-concept:C0391871,
umls-concept:C0542341,
umls-concept:C0680255,
umls-concept:C1136240,
umls-concept:C1283071,
umls-concept:C1963578
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pubmed:issue |
1
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pubmed:dateCreated |
1998-1-7
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pubmed:abstractText |
The use of bisindolylmaleimide derivatives of staurosporine as selective inhibitors of protein kinase C (PKC) is in doubt following the report by Alessi [FEBS Lett. 402 (1997) 121-123] that Ro31-8220 and GF109203X are potent in vitro inhibitors of p70 S6 kinase and mitogen-activated protein kinase-activated protein kinase-1beta, as well as of PKC. Here we show that the phorbol ester-stimulated release of choline- and ethanolamine-metabolites from C6 glioma cells due to phospholipid hydrolysis by phospholipase D (PLD) is not inhibited by rapamycin or PD98059, specific inhibitors respectively of p70 S6 kinase and MAPKK (MEK) and thus of MAPKAP kinase-1beta but is still completely blocked by Ro31-8220. We conclude therefore that p70S6k and MAPKAP kinase-1beta as well as MAPK are not involved in signalling pathways downstream of PKC that regulate phorbol ester-stimulated phospholipid turnover and that the inhibitory action of Ro31-8220 occurs by blocking PKC which regulates at least one pathway to PLD activation. The PI-3 kinase inhibitor, wortmannin, inhibits the phorbol ester-stimulated release of ethanolamine- but not choline-metabolites from C6 cells suggesting that different PLD isoforms regulate the turnover of PtdEth and PtdCho in C6 cells. Both PLD isoforms are activated via PKC but the PtdEth-PLD is also regulated via a wortmannin-sensitive pathway.
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pubmed:grant |
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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/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Choline,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamine,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase D,
http://linkedlifedata.com/resource/pubmed/chemical/Polyenes,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 90-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8220,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0014-5793
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
417
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38-42
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9395070-Androstadienes,
pubmed-meshheading:9395070-Animals,
pubmed-meshheading:9395070-Choline,
pubmed-meshheading:9395070-Enzyme Inhibitors,
pubmed-meshheading:9395070-Ethanolamine,
pubmed-meshheading:9395070-Flavonoids,
pubmed-meshheading:9395070-Glioma,
pubmed-meshheading:9395070-Indoles,
pubmed-meshheading:9395070-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:9395070-Phospholipase D,
pubmed-meshheading:9395070-Polyenes,
pubmed-meshheading:9395070-Protein Kinase C,
pubmed-meshheading:9395070-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9395070-Rats,
pubmed-meshheading:9395070-Ribosomal Protein S6 Kinases,
pubmed-meshheading:9395070-Ribosomal Protein S6 Kinases, 90-kDa,
pubmed-meshheading:9395070-Sirolimus,
pubmed-meshheading:9395070-Staurosporine,
pubmed-meshheading:9395070-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9395070-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Ro31-8220 inhibits protein kinase C to block the phorbol ester-stimulated release of choline- and ethanolamine-metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase-1beta do not function downstream of PKC in activating PLD.
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pubmed:affiliation |
Department of Biology, University of York, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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