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rdf:type |
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lifeskim:mentions |
umls-concept:C0026237,
umls-concept:C0031715,
umls-concept:C0109317,
umls-concept:C0376515,
umls-concept:C0441655,
umls-concept:C0449438,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1704708,
umls-concept:C1705767,
umls-concept:C1705791
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pubmed:issue |
1-3
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pubmed:dateCreated |
2004-6-30
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pubmed:abstractText |
Bcl-2 protein play important roles in the regulation of apoptosis. We previously reported that the phosphorylation of Bcl-2 was augmented by treatment with protein phosphatase 2A (PP2A) inhibitor; however, the kinase responsible for Bcl-2 phosphorylation had not yet been identified. In this study, we identified extracellular-signal-regulated kinase (ERK) as the responsible kinase for the phosphorylation of Bcl-2. We also found that the transmembrane region (TM) deleted form of Bcl-2 (Bcl-2DeltaTM), which was unable to localize on the mitochondria was constitutively phosphorylated, whereas wild-type Bcl-2 that localized on the mitochondria, was present in its hypophosphorylated form. The phosphorylation of Bcl-2DeltaTM was retarded by treatment with MAP kinase ERK kinase (MEK) inhibitor and PP2A did not bind to Bcl-2DeltaTM. These observations suggest that Bcl-2DeltaTM is constitutively phosphorylated by ERK, but is not dephosphorylated by PP2A in human tumor cell lines. The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
2
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pubmed:volume |
569
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
249-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15225643-Apoptosis,
pubmed-meshheading:15225643-Carcinoma, Hepatocellular,
pubmed-meshheading:15225643-Cell Line, Tumor,
pubmed-meshheading:15225643-Enzyme Inhibitors,
pubmed-meshheading:15225643-HeLa Cells,
pubmed-meshheading:15225643-Humans,
pubmed-meshheading:15225643-Kinetics,
pubmed-meshheading:15225643-Liver Neoplasms,
pubmed-meshheading:15225643-Mitochondria,
pubmed-meshheading:15225643-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15225643-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15225643-Mutagenesis,
pubmed-meshheading:15225643-Phosphoprotein Phosphatases,
pubmed-meshheading:15225643-Phosphorylation,
pubmed-meshheading:15225643-Plasmids,
pubmed-meshheading:15225643-Protein Phosphatase 2,
pubmed-meshheading:15225643-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15225643-Recombinant Proteins,
pubmed-meshheading:15225643-Sequence Deletion
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pubmed:year |
2004
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pubmed:articleTitle |
The phosphorylation status and anti-apoptotic activity of Bcl-2 are regulated by ERK and protein phosphatase 2A on the mitochondria.
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pubmed:affiliation |
Antibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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