Linked Life Data

12809513

Source:http://linkedlifedata.com/resource/pubmed/id/12809513

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-6-17
pubmed:abstractText
In CV-1 cells transfected with wild-type (wt) nuclear thyroid hormone receptor TRbeta1 (TR), L-thyroxine (T(4)) causes activation and nuclear translocation of mitogen-activated protein kinase (MAPK, ERK1/2), co-immunoprecipitation of MAPK and TR, and MAPK-dependent serine phosphorylation of TR. In the present studies, we have identified (1) the likely site of TR serine phosphorylation in the TR DNA-binding domain (DBD) by T(4)-activated MAPK, (2) the site of MAPK docking on TR induced by T(4), and (3) functional consequences of TR docking site and serine phosphorylation site mutations on co-repressor and co-activator binding and on transcriptional activation by wt and mutant receptors in T(4)-treated cells. Plasmids containing TR(wt), serine 142-substituted TR (TR(S142A) or TR(S142E)), TR(K128A), TR(R132A), or TR(R133A) were transfected into CV-1 cells, and the cells were treated with 10(-7) M T(4) for 30 min. Activated MAPK was present in nuclear fractions of all T(4)-treated cells and co-immunoprecipitated prominently with TR(wt), TR(S142A), and TR(S142E). TR(K128A) complexing with activated MAPK was minimally detectable, but no association of MAPK with TR(R132A) or TR(R133A) was seen in cells treated with T(4). Serine phosphorylation of TR(wt), but not of any mutants, occurred with T(4). In in vitro phosphorylation studies, constitutively activated MAPK phosphorylated only TR(wt). We concluded that serine 142 of the TR DBD is the likely site of phosphorylation by T(4)-activated MAPK and that the docking site on TR for activated MAPK includes residues 128-133 (KGFFRR), a basic amino acid-enriched motif novel for MAPK substrates. TR mutations in the proposed MAPK docking domain and at residue 142 modulated T(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of TR in a thyroid hormone response element-luciferase reporter assay.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7571-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12809513-Amino Acid Substitution, pubmed-meshheading:12809513-Animals, pubmed-meshheading:12809513-Binding Sites, pubmed-meshheading:12809513-Cell Line, pubmed-meshheading:12809513-Cell Nucleus, pubmed-meshheading:12809513-Cercopithecus aethiops, pubmed-meshheading:12809513-DNA-Binding Proteins, pubmed-meshheading:12809513-Enzyme Activation, pubmed-meshheading:12809513-Mitogen-Activated Protein Kinases, pubmed-meshheading:12809513-Mutation, pubmed-meshheading:12809513-Phosphorylation, pubmed-meshheading:12809513-Precipitin Tests, pubmed-meshheading:12809513-Protein Structure, Tertiary, pubmed-meshheading:12809513-Serine, pubmed-meshheading:12809513-Thyroid Hormone Receptors beta, pubmed-meshheading:12809513-Thyroxine, pubmed-meshheading:12809513-Transcriptional Activation, pubmed-meshheading:12809513-Transfection
pubmed:year
2003
pubmed:articleTitle
Identification of the putative MAP kinase docking site in the thyroid hormone receptor-beta1 DNA-binding domain: functional consequences of mutations at the docking site.
pubmed:affiliation
Stratton Veterans Affairs Medical Center, Albany, New York 12208, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't