Source:http://linkedlifedata.com/resource/pubmed/id/12356758
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
50
|
pubmed:dateCreated |
2002-12-9
|
pubmed:abstractText |
Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARgamma and other transcription factors. PBP is an integral component of a multiprotein thyroid hormone receptor-associated protein (TRAP)/vitamin D(3) receptor-interacting protein (DRIP)/activator-recruited cofactor (ARC) complex required for transcriptional activity. To study the regulation of PBP by cellular signaling pathways, we identified the phosphorylation sites of PBP. Using a combination of in vitro and in vivo approaches and mutagenesis of PBP phosphorylation sites, we identified six phosphorylation sites on PBP: one exclusive protein kinase A (PKA) phosphorylation site at serine 656, two protein kinase C (PKC) sites at serine 796 and serine 1345, a common PKA/PKC site at serine 756, and two extracellular signal-regulated kinase 2 sites of the mitogen-activated protein kinase (MAPK) family at threonine 1017 and threonine 1444. Binding of PBP to PPARgamma1 or retinoid-X-receptor for 9-cis-retinoic acid (RXR) is independent of their phosphorylation states, implying no changes in protein-protein interaction after modification by phosphorylation. Overexpression of RafBXB, an activated upstream kinase of the MAPK signal transduction pathway, exerts a significant additive inductive effect on PBP coactivator function. This effect is significantly diminished by overexpression of RafBXB301, a dominant negative mutant of RafBXB. These results identify phosphorylation as a regulatory modification event of PBP and demonstrate that PBP phosphorylation by Raf/MEK/MAPK cascade exerts a positive effect on PBP coactivator function. The functional role of PKA and PKC phosphorylation sites in PBP remains to be elucidated.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MED1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mediator Complex Subunit 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
13
|
pubmed:volume |
277
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
48745-54
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:12356758-Animals,
pubmed-meshheading:12356758-Base Sequence,
pubmed-meshheading:12356758-COS Cells,
pubmed-meshheading:12356758-Carrier Proteins,
pubmed-meshheading:12356758-HeLa Cells,
pubmed-meshheading:12356758-Humans,
pubmed-meshheading:12356758-Mediator Complex Subunit 1,
pubmed-meshheading:12356758-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12356758-Oligodeoxyribonucleotides,
pubmed-meshheading:12356758-Phosphorylation,
pubmed-meshheading:12356758-Recombinant Proteins,
pubmed-meshheading:12356758-Trans-Activators,
pubmed-meshheading:12356758-Transcription, Genetic,
pubmed-meshheading:12356758-Transcription Factors
|
pubmed:year |
2002
|
pubmed:articleTitle |
Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogen-activated protein kinase.
|
pubmed:affiliation |
Department of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|