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.
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Department of Tumor Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
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D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D009857:Oncogenes; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
D004121:Dimethyl Sulfoxide; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine