Epidermal Growth Factor Receptor Is Down-Regulated by a 10,400 MW Protein Encoded by the E3 Region of Adenovirus

Cell. 1989 Apr 7;57(1):135-44. doi: 10.1016/0092-8674(89)90179-7.

Abstract

Epidermal growth factor (EGF) binds to specific high affinity receptors (EGF-Rs) and induces endosome-specific internalization and degradation of ligand-receptor complexes in lysosomes. We report here that EGF-R is down-regulated in an analogous manner during early infection of a variety of cell types by group C human adenoviruses. This effect is not a function of viral entry, nor is it due to a nonspecific increase in turnover of membrane proteins. Using a series of virus deletion mutants, the gene responsible for EGF-R down-regulation was mapped to the E3 transcription unit. The E3 gene product, a protein of MW 10,400 (10.4K), induces internalization and degradation of EGF-R, but does not affect synthesis of the EGF-R precursor. The 10.4K protein is not an EGF-like autocrine growth factor, but is similar in sequence to a region in EGF-R at the cytoplasmic face of the transmembrane domain. This suggests that down-regulation of EGF-R during adenovirus infection may occur by a novel mechanism that involves the formation of hetero-oligomers composed of 10.4K and EGF-R.

Publication types

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

MeSH terms

  • Adenovirus Early Proteins
  • Adenoviruses, Human / genetics*
  • Amino Acid Sequence
  • Antigen-Antibody Complex
  • Cell Membrane / analysis
  • Cell Membrane / ultrastructure
  • Chromosome Mapping
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Expression Regulation
  • Genes, Regulator
  • Genes, Viral
  • Humans
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / analysis
  • Oncogene Proteins, Viral / pharmacology
  • Oncogene Proteins, Viral / physiology*
  • Precipitin Tests

Substances

  • Adenovirus Early Proteins
  • Antigen-Antibody Complex
  • Oncogene Proteins, Viral
  • ErbB Receptors