Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress

Mol Cell. 1999 Apr;3(4):521-6. doi: 10.1016/s1097-2765(00)80480-3.


Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that serves as an essential regulator of many hormone-induced genes in the vertebrate endocrine system. The apparent absence of a SF-1 ligand prompted speculation that this receptor is regulated by alternative mechanisms involving signal transduction pathways. Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway. We propose that this single modification of SF-1 and the subsequent recruitment of nuclear receptor cofactors couple extracellular signals to steroid and peptide hormone synthesis, thereby maintaining dynamic homeostatic responses in stress and reproduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Fushi Tarazu Transcription Factors
  • Genes, Reporter
  • Homeodomain Proteins
  • Humans
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Receptor Co-Repressor 2
  • Nuclear Receptor Coactivator 2
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repressor Proteins / metabolism
  • Reproduction
  • Serine / metabolism
  • Signal Transduction / physiology*
  • Steroidogenic Factor 1
  • Stress, Physiological
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • NCOR2 protein, human
  • NR5A1 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 2
  • Nuclear Receptor Coactivator 2
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Steroidogenic Factor 1
  • Transcription Factors
  • Serine
  • Epidermal Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases