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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6711
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pubmed:dateCreated |
1999-1-7
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pubmed:abstractText |
The protection against apoptosis provided by growth factors in several cell lines is due to stimulation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, which results in activation of protein kinase B (PKB; also known as c-Akt and Rac) and phosphorylation and sequestration to protein 14-3-3 of the proapoptotic Bcl-2-family member BAD. A modest increase in intracellular Ca2+ concentration also promotes survival of some cultured neurons through a pathway that requires calmodulin but is independent of PI(3)K and the MAP kinases. Here we report that Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK) activates PKB directly, resulting in phosphorylation of BAD on serine residue 136 and the interaction of BAD with protein 14-3-3. Serum withdrawal induced a three- to fourfold increase in cell death of NG108 neuroblastoma cells, and this apoptosis was largely blocked by increasing the intracellular Ca2+ concentration with NMDA (N-methyl-D-aspartate) or KCl or by transfection with constitutively active CaM-KK. The effect of NMDA on cell survival was blocked by transfection with dominant-negative forms of CaM-KK or PKB. These results identify a Ca2+-triggered signalling cascade in which CaM-KK activates PKB, which in turn phosphorylates BAD and protects cells from apoptosis.
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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/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
396
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
584-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9859994-Animals,
pubmed-meshheading:9859994-Binding Sites,
pubmed-meshheading:9859994-COS Cells,
pubmed-meshheading:9859994-Calcium,
pubmed-meshheading:9859994-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9859994-Carrier Proteins,
pubmed-meshheading:9859994-Cell Line,
pubmed-meshheading:9859994-Cell Survival,
pubmed-meshheading:9859994-Cloning, Molecular,
pubmed-meshheading:9859994-Enzyme Activation,
pubmed-meshheading:9859994-Mutagenesis,
pubmed-meshheading:9859994-Phosphorylation,
pubmed-meshheading:9859994-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9859994-Proto-Oncogene Proteins,
pubmed-meshheading:9859994-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:9859994-Rats,
pubmed-meshheading:9859994-Recombinant Fusion Proteins,
pubmed-meshheading:9859994-Transfection,
pubmed-meshheading:9859994-bcl-Associated Death Protein
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pubmed:year |
1998
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pubmed:articleTitle |
Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway.
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pubmed:affiliation |
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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