MAP Kinases Erk1/2 Phosphorylate Sterol Regulatory Element-binding Protein (SREBP)-1a at Serine 117 in Vitro*
- Resource Type
- Article
- Authors
- Roth, Gunther; Kotzka, Jörg; Kremer, Lorena; Lehr, Stefan; Lohaus, Christiane; Meyer, Helmut E.; Krone, Wilhelm; Müller-Wieland, Dirk
- Source
- Journal of Biological Chemistry; October 2000, Vol. 275 Issue: 43 p33302-33307, 6p
- Subject
- Language
- ISSN
- 00219258; 1083351X
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 vitromutagenesis. Mutation of serine 117 to alanine abolished Erk2-mediated phosphorylation in vitroand 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.