Prolonged activation of ERK2 by epidermal growth factor and other growth factors requires a functional insulin-like growth factor 1 receptor

Endocrinology. 1999 Jul;140(7):3163-9. doi: 10.1210/endo.140.7.6766.


We have investigated the activation of ERK2, a serine/threonine kinase necessary for transmission of mitogenic signals, in cells derived from mouse embryos homozygous for a null mutation of the insulin-like growth factor (IGF)-1R gene (R- cells) and from wild-type littermates (W cells), respectively. Stimulation of quiescent W cells with IGF-1, epidermal growth factor (EGF), or with a combination growth factors induced both a maximal transient and a prolonged activation of ERK2, whereas platelet-derived growth factor or a combination of platelet-derived growth factor and EGF resulted only in transient activation of ERK2. In contrast, stimulation of R cells with IGF-1, EGF, or combinations of growth factors resulted in a transient and submaximal activation of ERK2. Reintroduction of a wild-type human IGF-1R or of a C-terminus IGF-1R mutant, but not of a juxtamembrane mutant IGF-1R, into R- cells was able to restore ERK2 activation to wild-type levels. Thus, prolonged ERK2 activation in mouse embryo fibroblasts stimulated with purified growth factors is largely dependent on a signal generated by the IGF-1R.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation / physiology
  • Epidermal Growth Factor / pharmacology*
  • Growth Substances / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Peptide Fragments / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Receptors, Somatomedin / chemistry
  • Receptors, Somatomedin / metabolism
  • Receptors, Somatomedin / physiology*


  • Growth Substances
  • Peptide Fragments
  • Platelet-Derived Growth Factor
  • Receptors, Somatomedin
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1