Insulin-activated Erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding Protein-2 at serine residues 432 and 455 in vivo.

The transcription factor sterol regulatory element binding protein (SREBP)-2 plays a pivotal role in lipid metabolism. Previously, we have shown that the mature form of SREBP-2 is a substrate of Erk-mitogen-activated protein kinases (MAPK). The aim of the present study was to identify Erk-specific phosphorylation sites. Using a protein chemistry ...
approach, we could identify Ser-432 and Ser-455 as major phosphorylation sites. Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/DNA interaction, but enhances trans-activity. In intact cells, SREBP-2 is phosphorylated by insulin, which seems to be related to their bio-responses on low density lipoprotein receptor activity. These results suggest that activation of Erk-MAPK pathways by hormones such as insulin might be related to a novel regulatory principle of SREBP-2.
Mesh Terms:
Binding Sites, Blotting, Western, Cell Line, Chromatography, High Pressure Liquid, Cloning, Molecular, DNA, DNA-Binding Proteins, Genes, Reporter, Humans, Insulin, Luciferases, MAP Kinase Signaling System, Mitogen-Activated Protein Kinases, Mutagenesis, Site-Directed, Peptides, Phosphorylation, Plasmids, Promoter Regions, Genetic, Protein Structure, Tertiary, Serine, Sterol Regulatory Element Binding Protein 2, Transcription Factors, Transcriptional Activation, Transfection
J. Biol. Chem.
Date: May. 21, 2004
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