Expression of an altered epidermal growth factor receptor by human glioblastoma cells.

The expression and activities of epidermal growth factor (EGF) receptor and a highly related protein (Mr approximately 190,000 protein; p190) were characterized from a human glioma cell line, KE. p190 was specifically immunoprecipitated with a monoclonal antibody with specificity against the EGF receptor (Mr approximately 170,000; p170). Furthermore, both proteins were shown to possess tyrosine-protein kinase activities, although p170 required the presence of EGF to undergo autophosphorylation, whereas p190 appeared to be constitutively activated. Partial and total proteolytic polypeptide analyses of the two proteins suggested that their phosphopeptides were nearly identical and were phosphorylated on similar amino acid residues. However, a number of alterations were observed between [35S]methionine-labeled polypeptides of p170 and p190. This was also supported by the finding that the size of the protein cores of p170 and p190 was different. This observation is in agreement with Northern blot analysis in which KE cells expressed a novel EGF receptor RNA of 10.5 kilobases in addition to the previously reported 10-kilobase RNA. Southern blot analysis of the EGF receptor gene also revealed some amplification, approximately 4- to 5-fold; however, no significant rearrangements were noted in the KE cell DNA. These results suggest that p190 represents an endogeneous structurally and functionally altered EGF receptor.