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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1993-11-22
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pubmed:abstractText |
cis-Diamminedichloroplatinum(II) (CDDP) induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC-9 human lung cancer cells. Evidence for a phosphorylated p34cdc2 protein kinase complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 protein kinase appeared to be dephosphorylated at M phase. After exposure to CDDP in G1 phase, PC-9 cells were arrested in G2 phase. The activation of p34cdc2 protein kinase was inhibited by CDDP. Cyclin A and wee-I kinase were not affected by the exposure to CDDP. Cyclin B was degraded in M phase in PC-9 cells. Exposure to CDDP did not affect the degradation of cyclin B. Our data suggest that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34cdc2 protein kinase. To determine whether the p34cdc2 protein kinase is a primary target for CDDP, we examined the direct effect of CDDP on tyrosine dephosphorylation of p34cdc2 protein kinase in cellular extracts. Cell lysates from synchronized PC-9 in G2 phase were immunoprecipitated with p13-Sepharose beads. In vitro dephosphorylation of phosphotyrosine of p34cdc2 protein kinase was observed after exposure to okadaic acid in a concentration-dependent manner. The dephosphorylation of p34cdc2 protein kinase by okadaic acid was inhibited by CDDP. We hypothesize that inhibition of p34cdc2 dephorphorylation by CDDP is important for its growth-inhibiting properties.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC2 Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Organoplatinum Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/WEE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/didimethylsulfoxide...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
616-22
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8406990-CDC2 Protein Kinase,
pubmed-meshheading:8406990-Cell Cycle Proteins,
pubmed-meshheading:8406990-Cyclins,
pubmed-meshheading:8406990-G2 Phase,
pubmed-meshheading:8406990-Humans,
pubmed-meshheading:8406990-Immunoblotting,
pubmed-meshheading:8406990-Lung Neoplasms,
pubmed-meshheading:8406990-Mitosis,
pubmed-meshheading:8406990-Nuclear Proteins,
pubmed-meshheading:8406990-Organoplatinum Compounds,
pubmed-meshheading:8406990-Phosphorylation,
pubmed-meshheading:8406990-Protein Kinases,
pubmed-meshheading:8406990-Protein-Tyrosine Kinases,
pubmed-meshheading:8406990-Tumor Cells, Cultured
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pubmed:year |
1993
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pubmed:articleTitle |
Cis-diamminedichloroplatinum(II) inhibits p34cdc2 protein kinase in human lung-cancer cells.
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pubmed:affiliation |
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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