Epidermal growth factor receptor is down-regulated by a 10,400 MW protein encoded by the E3 region of adenovirus.
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.
Carlin
C R
CR
Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110.
Tollefson
A E
AE
Brady
H A
HA
Hoffman
B L
BL
Wold
W S
WS
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex; D002462:Cell Membrane / Q000032:analysis / Q000648:ultrastructure; D002874:Chromosome Mapping; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D005814:Genes, Viral; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D011233:Precipitin Tests
D017456:Adenovirus Early Proteins; D000936:Antigen-Antibody Complex; D009856:Oncogene Proteins, Viral; D066246:ErbB Receptors