Tyrosine protein kinase in preneoplastic and neoplastic rat liver

When rats are subjected to chemical hepatocarcinogenesis according to the protocol of D. Solt and E. Farber ((1976) Nature (London) 263, 701-703), the liver exhibits elevated levels of tyrosine protein kinase activity as early as 3 weeks after the injection of diethylnitrosoamine. A more striking elevation in tyrosine protein kinase activity is noted in rat hepatomas induced by administration of chemical carcinogens, in particular that of 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB). Tyrosine protein kinase solubilized from the particulate fraction of 3′-Me-DAB-induced hepatoma has a molecular weight identical to that of p60^v-src, cross-reacts with p60^v-src immunologically, phosphorylates the heavy chain of anti-p60^v-src IgG, and probably belongs to a family of p60^c-src. The tyrosine protein kinase from the particulate fraction of normal rat liver is indistinguishable from the hepatoma kinase in these properties; thus it apparently differs only in the level of activity. Whether the liver and hepatoma kinases differ merely quantitatively or whether they differ even qualitatively, however, remains to be elucidated.