Inhibition of epidermal growth factor-induced phosphorylation by trifluoperazine.
We studied the effects of a series of drugs on A431, a cell line with well-characterized growth factor requirements and epidermal growth factor (EGF) receptors. The major [32PO4]-labeled protein immunoprecipitated with anti-phosphotyrosine antibodies from EGF-stimulated A431 cells was the EGF receptor. Both the quantity of [32PO4]-labeled EGF receptor immunoprecipitated and the phosphotyrosine content of total [32PO4]-labeled proteins were reduced by the addition during EGF stimulation of trifluoperazine (TFP). TFP had little effect on the binding, internalization, and processing of [125I]-EGF. In addition to the effects on phosphorylation, TFP inhibited cell growth both in the presence and absence of EGF. Morphologically, TFP blocked EGF-induced ruffling. TFP did not alter the EGF-stimulated phosphatidylinositol turnover. In an in vitro experiment using A431 cell membranes, TFP did not inhibit phosphorylation of the EGF receptor.
A H
AH
Ross
C
C
Damsky
P D
PD
Phillips
F
F
Hwang
P
P
Vance
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors; D007099:Imipramine / Q000494:pharmacology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010766:Phosphorylation; D019000:Phosphotyrosine; D011956:Receptors, Cell Surface / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D013449:Sulfonamides; D014268:Trifluoperazine; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; C017967:W 7; D066246:ErbB Receptors; D007099:Imipramine; D002746:Chlorpromazine