Mitogen-activated protein kinase stimulation by a tyrosine kinase-negative epidermal growth factor receptor

J Biol Chem. 1993 Jan 25;268(3):2250-4.


Mutation of the epidermal growth factor receptor (EGF-R) within the ATP binding subdomain results in a receptor that lacks tyrosine kinase activity and is defective in signal transduction. However, this kinase-negative EGF-R is able to activate MAP kinase (Campos-Gonzalez, R., and Glenny, J. R. (1992) J. Biol. Chem. 267, 14535-14538). This observation suggests that signal initiation by the EGF-R can occur by a mechanism that is independent of the receptor tyrosine kinase activity. Here, we report that the kinase-negative EGF-R is phosphorylated on tyrosine in EGF-treated cells. The mechanism of tyrosine phosphorylation can be accounted for by the action of EGF to stimulate a protein kinase activity that is associated with the kinase-negative EGF-R. This protein kinase activity is not intrinsic to the receptor and can be separated from the EGF-R by incubation with 0.5 M NaCl. MAP kinase activation by the kinase-negative EGF-R may therefore occur by a mechanism that requires a receptor-associated tyrosine kinase. Thus, it is unnecessary to propose a novel kinase-independent mechanism of signal initiation to account for MAP kinase activation by the kinase-negative EGF-R.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cricetinae
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology*
  • Gene Expression
  • Humans
  • Mitogens / pharmacology*
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphorylation
  • Phosphotyrosine
  • Protein Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / physiology
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Mitogens
  • Phosphotyrosine
  • Tyrosine
  • Epidermal Growth Factor
  • Protein Kinases
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases