Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Epidermal Growth Factor / pharmacology
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Fushi Tarazu Transcription Factors
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Genes, Reporter
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Homeodomain Proteins
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Humans
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Mutation
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Nuclear Proteins / genetics
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Nuclear Receptor Co-Repressor 2
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Nuclear Receptor Coactivator 2
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Phosphorylation
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Protein Processing, Post-Translational
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Repressor Proteins / metabolism
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Reproduction
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Serine / metabolism
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Signal Transduction / physiology*
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Steroidogenic Factor 1
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Stress, Physiological
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Fushi Tarazu Transcription Factors
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Homeodomain Proteins
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NCOR2 protein, human
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NR5A1 protein, human
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 2
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Nuclear Receptor Coactivator 2
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Receptors, Cytoplasmic and Nuclear
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Repressor Proteins
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Steroidogenic Factor 1
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Transcription Factors
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Serine
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Epidermal Growth Factor
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Calcium-Calmodulin-Dependent Protein Kinases