Abstract
Sterol regulatory element-binding protein (SREBP)-1a is a transcription factor sensing cellular cholesterol levels and integrating gene regulatory signals mediated by MAP kinase cascades. Here we report the identification of serine 117 in SREBP-1a as the major phosphorylation site of the MAP kinases Erk1/2. This site was identified by nanoelectrospray mass spectrometry and peptide sequencing of recombinant fusion proteins phosphorylated by Erk1/2 in vitro. Serine 117 was verified as the major phosphorylation site by in vitro mutagenesis. Mutation of serine 117 to alanine abolished Erk2-mediated phosphorylation in vitro and the MAP kinase-related transcriptional activation of SREBP-1a by insulin and platelet-derived growth factor in vivo. Our data indicate that the MAP kinase-mediated effects on SREBP-1a-regulated target genes are linked to this phosphorylation site.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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CCAAT-Enhancer-Binding Proteins / chemistry
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CCAAT-Enhancer-Binding Proteins / metabolism*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Humans
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Insulin / pharmacology
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Mitogen-Activated Protein Kinase 1 / physiology*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / physiology*
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Molecular Sequence Data
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Phosphorylation
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Platelet-Derived Growth Factor / pharmacology
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Receptors, LDL / genetics
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Serine / metabolism
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors*
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Insulin
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Platelet-Derived Growth Factor
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Receptors, LDL
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors
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Serine
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases