Truncation of the human EGF receptor leads to differential transforming potentials in primary avian fibroblasts and erythroblasts

EMBO J. 1988 Oct;7(10):3061-71.

Abstract

The transforming capacity of the normal and mutant human EGF receptor (EGFR) was investigated in primary chicken cells. In fibroblasts, both N- and C-terminal truncations resulted in a weak, additive oncogenic activity. However, not even double truncations caused a v-erbB-like phenotype. Upon EGF-binding, on the other hand, both normal and C-terminally truncated EGFRs resembled v-erbB in their fibroblast transforming potential. In erythroblasts, N-terminal truncation was sufficient to induce constitutive self-renewal, which was enhanced by deletion of 32 C-terminal amino acids but abolished by a larger truncation of 202 amino acids. In contrast to the normal EGFR, the receptor lacking 32 C-terminal amino acids resembled v-erbB in conferring erythropoietin independence for spontaneous differentiation to the transformed erythroblasts. Our results indicate that the C-terminal domain of the EGFR is non-essential in fibroblast transformation, but seems to be crucial for both self renewal induction and specificity of receptor function in erythroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Division
  • Cell Transformation, Neoplastic / etiology*
  • Cells, Cultured
  • Chickens
  • DNA Mutational Analysis
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology*
  • Erythroblasts
  • Erythropoietin / pharmacology
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Leukemia, Experimental / genetics
  • Mitosis
  • Oncogene Proteins, Viral / genetics
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Oncogene Proteins, Viral
  • Erythropoietin
  • Epidermal Growth Factor
  • ErbB Receptors