Ethanol-induced structural and functional alterations of epidermal growth factor receptor in buccal mucosa.
1. Ethanol treatment caused a 47% decrease in [125I]EGF binding to the membrane preparations of buccal mucosa resulting from the decrease of binding sites rather than the affinity of high affinity receptor. 2. The immunoblot revealed a protein band of 170 kDa in the control sample, while a barely detectable 200 kDa protein was observed in the ethanol-treated sample. 3. Protein kinase assays using [32P]ATP as probe showed an EGF-stimulated phosphorylation band of 170 kDa in the control but not in ethanol-treated sample. 4. Ethanol did not change the basal incorporation of [3H]thymidine and [35S]methionine, but caused a 38% and 57% decrease of EGF-stimulated thymidine and methionine incorporation, respectively. 5. The data suggest that EtOH decreases EGF receptor binding through modification of the receptor molecule, thereby impairing receptor kinase activity and its physiological function.
Wang
S L
SL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
Jacober
L
L
Wu-Wang
C Y
CY
Slomiany
A
A
Slomiany
B L
BL
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D000431:Ethanol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors