Linked Life Data

14978034

Source:http://linkedlifedata.com/resource/pubmed/id/14978034

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2004-5-10
pubmed:abstractText
We delineate a mechanism by which dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD)-mediated formation of the aryl hydrocarbon receptor (AhR) DNA binding complex is disrupted by a single mutation at the conserved AhR tyrosine 9. Replacement of tyrosine 9 with the structurally conservative phenylalanine (AhRY9F) abolished binding to dioxin response element (DRE) D, E, and A and abrogated DRE-driven gene induction mediated by the AhR with no effect on TCDD binding, TCDD-induced nuclear localization, or ARNT heterodimerization. The speculated role for phosphorylation at tyrosine 9 was also examined. Anti-phosphotyrosine immunoblotting could not detect a major difference between the AhRY9F mutant and wild-type AhR, but a basic isoelectric point shift was detected by two-dimensional gel electrophoresis of AhRY9F. However, an antibody raised to recognize only phosphorylated tyrosine 9 (anti-AhRpY9) confirmed that AhR tyrosine 9 is not a phosphorylated residue required for DRE binding. Kinase assays using synthetic peptides corresponding to the wild-type and mutant AhR residues 1-23 demonstrated that a tyrosine at position 9 is important for substrate recognition at serine(s)/threonine(s) within this sequence by purified protein kinase C (PKC). Also, compared with AhRY9F, immunopurified full-length wild-type receptor was more rapidly phosphorylated by PKC. Furthermore, co-treatment of AhR-deficient cells that expressed AhRY9F and a DRE-driven luciferase construct with phorbol 12-myristate 13-acetate and TCDD resulted in a 30% increase in luciferase activity compared with AhRY9F treated with TCDD alone. Overall, AhR tyrosine 9, which is not a phosphorylated residue itself but is required for DNA binding, appears to play a crucial role in AhR activity by permitting proper phosphorylation of the AhR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20582-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14978034-Amino Acid Substitution, pubmed-meshheading:14978034-Animals, pubmed-meshheading:14978034-Base Sequence, pubmed-meshheading:14978034-Binding Sites, pubmed-meshheading:14978034-Conserved Sequence, pubmed-meshheading:14978034-DNA Primers, pubmed-meshheading:14978034-DNA-Binding Proteins, pubmed-meshheading:14978034-Dimerization, pubmed-meshheading:14978034-Green Fluorescent Proteins, pubmed-meshheading:14978034-HeLa Cells, pubmed-meshheading:14978034-Humans, pubmed-meshheading:14978034-Kinetics, pubmed-meshheading:14978034-Luminescent Proteins, pubmed-meshheading:14978034-Mice, pubmed-meshheading:14978034-Mutagenesis, Site-Directed, pubmed-meshheading:14978034-Phosphorylation, pubmed-meshheading:14978034-Phosphotyrosine, pubmed-meshheading:14978034-Receptors, Aryl Hydrocarbon, pubmed-meshheading:14978034-Recombinant Fusion Proteins, pubmed-meshheading:14978034-Tetrachlorodibenzodioxin, pubmed-meshheading:14978034-Tyrosine
pubmed:year
2004
pubmed:articleTitle
The aryl hydrocarbon receptor (AhR) tyrosine 9, a residue that is essential for AhR DNA binding activity, is not a phosphoresidue but augments AhR phosphorylation.
pubmed:affiliation
Department of Environmental Medicine, School of Medicine, University of Rochester, 575 Elmwood Avenue, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.