ACCELERATED DEGRADATION OF 160 KDA EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR PRECURSOR BY THE TYROSINE KINASE INHIBITOR HERBIMYCIN-A IN THE ENDOPLASMIC-RETICULUM OF A431 HUMAN EPIDERMOID CARCINOMA-CELLS

The effect of herbimycin A on the biosynthesis of epidermal growth fac tor (EGF) receptor was examined in human epidermoid carcinoma A431 cel ls. Cells were pulse-labelled with [S-35]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an imma ture 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the a bsence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the syn thesis of the secreted form of EGF receptor devoid of cytoplasmic doma in, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhib ited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H di gestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A s electively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aber rant molecule which was subjected to rapid degradation in the endoplas mic reticulum.