Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress
| Autor: | G D, Hammer, I, Krylova, Y, Zhang, B D, Darimont, K, Simpson, N L, Weigel, H A, Ingraham |
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| Rok vydání: | 1999 |
| Předmět: |
Homeodomain Proteins
Transcriptional Activation Epidermal Growth Factor Reproduction Fushi Tarazu Transcription Factors Nuclear Proteins Receptors Cytoplasmic and Nuclear Steroidogenic Factor 1 Transfection DNA-Binding Proteins Repressor Proteins Nuclear Receptor Coactivator 2 Genes Reporter Stress Physiological Calcium-Calmodulin-Dependent Protein Kinases Mutation Serine Tumor Cells Cultured Humans Nuclear Receptor Co-Repressor 2 Phosphorylation Protein Processing Post-Translational Signal Transduction Transcription Factors |
| Zdroj: | Molecular cell. 3(4) |
| ISSN: | 1097-2765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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