ADD1/SREBP-1c mediates insulin-induced gene expression linked to the MAP kinase pathway

Biochem Biophys Res Commun. 1998 Aug 19;249(2):375-9. doi: 10.1006/bbrc.1998.9161.

Abstract

The aim of this study was to define the role of sterol regulatory element binding protein (SREBP)-1c, the human homologue to ADD1 (adipocyte determination- and differentiation-dependent factor 1), in insulin-induced gene expression. Transfection studies using SREBP-1-deficient cells and a LDL receptor promoter fragment containing the ADD1/SREBP-1c binding side showed that the effects of insulin and PDGF were abolished compared to control cells and completely reconstituted by overexpressing ADD1/SREBP-1c. Overexpression of upstream activators of MAP kinases, like MEKK1 or MEK1, demonstrated that ADD1/SREBP-1c-mediated effects of insulin and PDGF might be linked to the MAP kinase cascade. The recombinant N-terminal domain of ADD1/SREBP-1c was phosphorylated predominantly on serine and slightly on threonine residues by MAP kinases ERK1 and ERK2 in vitro. This was reversible by alkaline phosphatase. We conclude that ADD1/SREBP-1c mediates gene regulatory effects of insulin as well as PDGF and that this signalling is linked to the MAP kinase cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / pharmacology
  • CCAAT-Enhancer-Binding Proteins*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Enzyme Activation
  • Gene Expression Regulation / drug effects*
  • Humans
  • Insulin / pharmacology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Phosphoserine / analysis
  • Phosphothreonine / analysis
  • Platelet-Derived Growth Factor / pharmacology
  • Promoter Regions, Genetic
  • Receptors, LDL / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors*
  • Transfection

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Insulin
  • Nuclear Proteins
  • Peptide Fragments
  • Platelet-Derived Growth Factor
  • Receptors, LDL
  • Recombinant Proteins
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Phosphothreonine
  • Phosphoserine
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Alkaline Phosphatase