dlk modulates mitogen-activated protein kinase signaling to allow or prevent differentiation

Exp Cell Res. 2002 Apr 1;274(2):178-88. doi: 10.1006/excr.2001.5464.

Abstract

The EGF-like membrane protein dlk plays a crucial role in the control of cell differentiation. Overexpression of the protein prevents, whereas inhibition of its expression increases, adipocyte differentiation of 3T3-L1 cells in response to Insulin-like Growth Factor I (IGF-1) or insulin. We have investigated whether dlk modulates the signaling pathways known to control this process. We found that the levels of dlk expression modulated signaling through the IGF-1 receptor, causing changes in the activation levels and kinetics of Extracellular-Regulated Kinase/Mitogen-Activated Protein Kinase (ERK/MAPK) that correlated with differentiation outcome. These changes occurred in response to IGF-1 or insulin but not in response to Epidermal Growth Factor. However, the levels of expression of IGF-1 receptor, or the activation of Insulin Receptor Substrate-1 in response to IGF-1, were not affected by the levels of dlk expression. Therefore, dlk appears to modulate ERK/MAPK signaling in response to specific differentiation signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptor, IGF Type 1 / drug effects
  • Receptor, IGF Type 1 / metabolism*

Substances

  • Enzyme Inhibitors
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • delta protein
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Mitogen-Activated Protein Kinases