Liver phosphotyrosine protein phosphatase and tyrosine protein kinase in chemical hepatocarcinogenesis

We found and characterized three forms of phosphotyrosine protein phosphatase, subsequently designated PTPP-1, -2 and -3, respectively, in rat liver. Chemical hepatocarcinogenesis according to Solt and Farber was accompanied by a slight increase in liver phosphotyrosine protein phosphatase activity and a remarkable increase in liver tyrosine protein kinase activity. A maximum 8-fold increase in tyrosine kinase activity was observed in hepatomas induced with 3'-methyl-4-dimethylaminoazobenzene (MeDAB). Tyrosine protein kinase that increased with the progress of chemical hepatocarcinogenesis was solubilized from the particulate fraction of MeDAB-induced hepatoma. The enzyme was shown to require Mg2+ for its activity, to immunoprecipitate with anti-pp-60src-IgG and to phosphorylate the IgG. Rat liver also contains another tyrosine protein kinase which requires Mn2+ and does not immunoprecipitate with anti-pp60src; the level of this enzyme appears to diminish with the progress of chemical hepatocarcinogenesis.