PMID- 10230404 OWN - NLM STAT- MEDLINE DCOM- 19990527 LR - 20190915 IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 3 IP - 4 DP - 1999 Apr TI - Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1. PG - 513-9 AB - 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. FAU - Tremblay, A AU - Tremblay A AD - Molecular Oncology Group, McGill University Health Centre, Montreal, Quebec, Canada. FAU - Tremblay, G B AU - Tremblay GB FAU - Labrie, F AU - Labrie F FAU - Giguere, V AU - Giguere V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (Estrogen Receptor beta) RN - 0 (Ifngr2 protein, mouse) RN - 0 (Ligands) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Interferon) RN - 0 (Transcription Factors) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (Ncoa1 protein, mouse) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - COS Cells MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Epidermal Growth Factor/pharmacology MH - Estrogen Receptor beta MH - Gene Expression Regulation/genetics MH - Genes, Reporter MH - Histone Acetyltransferases MH - Ligands MH - Mice MH - Molecular Sequence Data MH - Mutation MH - Nuclear Receptor Coactivator 1 MH - Phosphorylation MH - Receptors, Estrogen/genetics/*metabolism MH - Receptors, Interferon/*metabolism MH - Signal Transduction MH - Transcription Factors/*metabolism MH - Transfection EDAT- 1999/05/07 00:00 MHDA- 1999/05/07 00:01 CRDT- 1999/05/07 00:00 PHST- 1999/05/07 00:00 [pubmed] PHST- 1999/05/07 00:01 [medline] PHST- 1999/05/07 00:00 [entrez] AID - S1097-2765(00)80479-7 [pii] AID - 10.1016/s1097-2765(00)80479-7 [doi] PST - ppublish SO - Mol Cell. 1999 Apr;3(4):513-9. doi: 10.1016/s1097-2765(00)80479-7.