Suppressed autophosphorylation and tyrosine kinase-activity in revertant cell-lines expressing rat Neu oncogene

The revertants of neu oncogene-transformed cell lines, neu-R1 and neu-R2, have been shown previously to be phenotypically and morphologically nontransformed, yet both expressed the rat neu oncogene. In both cell lines the rat neu lacked significant tyrosine phosphorylation. We show that the intrinsic tyrosine kinase activity of neu-encoded p185 protein of both revertants was suppressed as well, and the p185 neu protein contained extracellular conformational changes that may inhibit receptor activity. Five other revertant cell lines that lost neu upon reversion were transfected with a rat neu oncogenic construct. They remained nontransforned but expressed the oncogene. Like neu-R1 and neu-R2, the transfectants expressed p185 that lacked receptor tyrosine phosphorylation. The inability of neu to induce transformation in these cell lines may be through a common mechanism that suppresses receptor autophosphorylation and tyrosine kinase activity.