Ligand-independent Recruitment of SRC-1 to Estrogen Receptor Beta Through Phosphorylation of Activation Function AF-1

Mol Cell. 1999 Apr;3(4):513-9. doi: 10.1016/s1097-2765(00)80479-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Epidermal Growth Factor / pharmacology
  • Estrogen Receptor beta
  • Gene Expression Regulation / genetics
  • Genes, Reporter
  • Histone Acetyltransferases
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Nuclear Receptor Coactivator 1
  • Phosphorylation
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Interferon / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Estrogen Receptor beta
  • Ifngr2 protein, mouse
  • Ligands
  • Receptors, Estrogen
  • Receptors, Interferon
  • Transcription Factors
  • Epidermal Growth Factor
  • Histone Acetyltransferases
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1
  • Calcium-Calmodulin-Dependent Protein Kinases