Maturation and externalization of EGF-receptor: a cell-surface located oncoprotein.
The EGF-receptor is a proto-oncogene encoded membrane protein related to the verb-B oncogene product of avian erythroblastosis virus. Here we report studies on expression and maturation characteristics of this receptor. The expression of intact 170 kDa EGF-receptor as well as a 100 kDa homologue that contains only the external domain is enhanced by the ligand EGF. EGF acts at transcriptional and post-transcriptional levels. To dissociate these pre-translational effects and the effects of EGF on receptor polypeptide synthesis from those on receptor export, pulse-chase experiments were conducted. These studies indicate that EGF stimulates post-translational transport and processing of the receptor, and this stimulation can occur in the absence of new protein synthesis. Other studies show that EGF accelerates at least two slow events in receptor maturation--the deoxynojirimycin-sensitive processing in endoplasmic reticulum (ER) and the swainsonine-sensitive processing in golgi, suggesting that EGF may influence one or more of the rate determining steps that control receptor export from ER. Overall the results demonstrate that EGF controls EGF-receptor expression at multiple levels, viz. at transcriptional, pre-translational and post-translational pathways of receptor biosynthesis.
Das
M
M
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6059.
Khire
J
J
Kesavan
P
P
D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006056:Golgi Apparatus / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D008565:Membrane Proteins; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D004815:Epidermal Growth Factor; D066246:ErbB Receptors