Repression of neu-induced clonogenicity by dimethylsulfoxide correlates with decreased levels of neu-encoded cell-surface p185 and changes in phosphotyrosine content of endogenous proteins.

Treatment of neu-transformed fibroblasts with dimethylsulfoxide (DMSO), results in change in morphology and loss of clonogenicity. Although the total amount of neu-encoded p185 protein and mRNA remained constant after DMSO treatment, cell-surface p185 decreased by 60%, indicating that transmembrane p185 protein is not located in its physiological position. The aberrant location of p185 induced by DMSO resulted in increased tyrosine phosphorylation of p185 and concomitant decreased tyrosine phosphorylation of potential substrate proteins of p185 in the cell. However, the autophosphorylation activity of p185 in vitro was unaffected by DMSO. Thus, DMSO-induced loss of clonogenicity may be due to inappropriate location of p185, which prevents interaction between p185 and its substrates and therefore inhibits p185-mediated signal transduction pathway.