Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1.
The estrogen receptors (ERs) alpha and beta possess a constitutive N-terminal activation function (AF-1) whose activity can be modulated by kinase signalling pathways. We demonstrate here that phosphorylation of AF-1 by MAP kinase (MAPK) leads to the recruitment of steroid receptor coactivator-1 (SRC-1) by ER beta in vitro. Enhancement of the interaction between SRC-1 and ER beta AF-1 is also observed in vivo in cells either treated with EGF or expressing activated Ras. Two serine residues in ER beta AF-1, of which one is contained within a motif present in other steroid receptors, are critical for physical interaction with SRC-1 and transcriptional activation. Our results establish a role for nuclear receptor phosphorylation in the recruitment of SRC-1 and provide a molecular basis for ligand-independent activation by ER beta via the MAPK pathway.
Tremblay
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A
Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada.
Tremblay
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GB
Labrie
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Giguère
V
V
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D047629:Estrogen Receptor beta; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D056920:Nuclear Receptor Coactivator 1; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D047629:Estrogen Receptor beta; C490116:Ifngr2 protein, mouse; D008024:Ligands; D011960:Receptors, Estrogen; D017471:Receptors, Interferon; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases