Retention of epidermal growth factor receptors in the endoplasmic reticulum of adenovirus-infected cells.
The epidermal growth factor (EGF) receptor is down-regulated during early infection with adenovirus, and this has been attributed to accelerated internalization and degradation of the receptor in the absence of ligand (Carlin, Tollefson, Brady, Hoffman & Wold (1989) Cell 57, 135-144]. Using pulse-chase analysis, we show that loss of functional EGF receptors after infection of human KB and A431 cells with adenovirus type 5 is accompanied by accumulation of a receptor precursor that remains fully sensitive to endoglycosidase H, indicative of retention in the endoplasmic reticulum. A truncated receptor, normally secreted by A431 cells, also accumulates intracellularly as an endoglycosidase H-sensitive precursor. In no case is the block in intracellular transport of EGF receptors complete. We conclude that both stimulation of EGF receptor internalization and degradation and inhibition of intracellular transport of newly synthesized EGF receptors from the endoplasmic reticulum towards the cell surface contribute to EGF receptor down-regulation in adenovirus-infected cells.
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
G F
GF
Verheijden
W H
WH
Moolenaar
H L
HL
Ploegh
D000260:Adenoviruses, Human / Q000235:genetics*; D002294:Carcinoma, Squamous Cell; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D009844:Oligosaccharides / Q000378:metabolism; D019000:Phosphotyrosine; D011990:Receptors, Transferrin / Q000096:biosynthesis; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D015395:Histocompatibility Antigens Class I; D009844:Oligosaccharides; D011990:Receptors, Transferrin; D019000:Phosphotyrosine; D014443:Tyrosine; D066246:ErbB Receptors