Epidermal Growth Factor Receptor Cytoplasmic Domain Mutations Trigger Ligand-Independent Transformation

Sharon Massoglia, Alane Gray, Thomas J. Dull, Susan Munemitsu, Hsing Jien Kung, Joseph Schlessinger, Axel Ullrich

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The transforming gene product of avian erythroblastosis virus, v-erbB, is derived from the epidermal growth factor (EGF) receptor but has lost its extracellular ligand-binding domain and was mutated in its cytoplasmic portion, which is thought to be responsible for biological signal generation. We have repaired the deletion of extracellular EGF-binding sequences and investigated the functional consequences of cytoplasmic erbB mutations. Within the resulting EGF receptors, the autophosphorylation activities of the cytoplasmic domains of v-erbB-H and v-erbB-ES4 were fully ligand dependent in intact cells. However, the mitogenic and transforming signaling activities of an EGF receptor carrying v-erbB-ES4 (but not v-erbB-H) cytoplasmic sequences remained ligand independent, whereas those of a receptor with a v-erbB-H cytoplasmic domain were regulated by EGF or transforming growth factor α. Thus, structural alterations in the cytoplasmic domain of growth factor receptor tyrosine kinases may induce constitutive signaling activity without autophosphorylation. These findings provide new insight into the mechanism of receptor-mediated signal transduction and suggest a novel alternative for subversion of cellular control mechanisms and proto-oncogene activation.

Original languageEnglish
Pages (from-to)3048-3055
Number of pages8
JournalMolecular and Cellular Biology
Volume10
Issue number6
DOIs
Publication statusPublished - Jan 1 1990
Externally publishedYes

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Epidermal Growth Factor Receptor
Ligands
Epidermal Growth Factor
Mutation
Alpharetrovirus
Growth Factor Receptors
Proto-Oncogenes
Transforming Growth Factors
Oncogenes
Protein-Tyrosine Kinases
Signal Transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Epidermal Growth Factor Receptor Cytoplasmic Domain Mutations Trigger Ligand-Independent Transformation. / Massoglia, Sharon; Gray, Alane; Dull, Thomas J.; Munemitsu, Susan; Kung, Hsing Jien; Schlessinger, Joseph; Ullrich, Axel.

In: Molecular and Cellular Biology, Vol. 10, No. 6, 01.01.1990, p. 3048-3055.

Research output: Contribution to journalArticle

Massoglia, Sharon ; Gray, Alane ; Dull, Thomas J. ; Munemitsu, Susan ; Kung, Hsing Jien ; Schlessinger, Joseph ; Ullrich, Axel. / Epidermal Growth Factor Receptor Cytoplasmic Domain Mutations Trigger Ligand-Independent Transformation. In: Molecular and Cellular Biology. 1990 ; Vol. 10, No. 6. pp. 3048-3055.
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