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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2000-9-14
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pubmed:abstractText |
The Bcl-2 family protein BAD promotes apoptosis by binding through its BH3 domain to Bcl-x(L) and related cell death suppressors. When BAD is phosphorylated on either Ser(112) or Ser(136), it forms a complex with 14-3-3 in the cytosol and no longer interacts with Bcl-x(L) at the mitochondria. Here we show that phosphorylation of a distinct site Ser(155), which is at the center of the BAD BH3 domain, directly suppressed the pro-apoptotic function of BAD by eliminating its affinity for Bcl-x(L). Protein kinase A functioned as a BAD Ser(155) kinase both in vitro and in cells. BAD Ser(155) was found to be a major site of phosphorylation induced following stimulation by growth factors and prevented by protein kinase A inhibitors but not by inhibitors of the phosphatidylinositol 3-kinase/Akt pathway. Growth factors inhibited BAD-induced apoptosis in both a Ser(112)/Ser(136)- and a Ser(155)-dependent fashion. Thus, growth factors engage an anti-apoptotic signaling pathway that inactivates BAD by direct modification of its BH3 cell death effector domain.
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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/BAD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25046-51
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10837473-Amino Acid Sequence,
pubmed-meshheading:10837473-Animals,
pubmed-meshheading:10837473-Apoptosis,
pubmed-meshheading:10837473-Binding Sites,
pubmed-meshheading:10837473-COS Cells,
pubmed-meshheading:10837473-Carrier Proteins,
pubmed-meshheading:10837473-Cell Death,
pubmed-meshheading:10837473-Cell Line,
pubmed-meshheading:10837473-Cell Survival,
pubmed-meshheading:10837473-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10837473-Dimerization,
pubmed-meshheading:10837473-Epidermal Growth Factor,
pubmed-meshheading:10837473-Growth Substances,
pubmed-meshheading:10837473-HeLa Cells,
pubmed-meshheading:10837473-Humans,
pubmed-meshheading:10837473-Phosphorylation,
pubmed-meshheading:10837473-Platelet-Derived Growth Factor,
pubmed-meshheading:10837473-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10837473-Rats,
pubmed-meshheading:10837473-Recombinant Proteins,
pubmed-meshheading:10837473-Sequence Alignment,
pubmed-meshheading:10837473-Sequence Homology, Amino Acid,
pubmed-meshheading:10837473-Serine,
pubmed-meshheading:10837473-Transfection,
pubmed-meshheading:10837473-bcl-Associated Death Protein,
pubmed-meshheading:10837473-bcl-X Protein
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pubmed:year |
2000
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pubmed:articleTitle |
Growth factors inactivate the cell death promoter BAD by phosphorylation of its BH3 domain on Ser155.
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pubmed:affiliation |
Apoptosis Technology, Inc., Cambridge, Massachusetts 02139, USA. xiao-mai.zhou@immunogen.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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