DAUNOMYCIN INHIBITS INSULIN-LIKE GROWTH-FACTOR I-DEPENDENT PROTEIN-TYROSINE PHOSPHORYLATION

The effect of the antitumor antibiotic daunomycin (DN) was studied on insulin-like growth factor I (IGF-I)-dependent protein tyrosine phosph orylation. DN was found to inhibit IGF-I-dependent phosphorylation of the artificial substrate poly(Glu:Tyr)(4:1) by intrinsic IGF-I recepto r kinase either from mouse cerebellum or from rat spinal cord. IGF-I-d ependent autophosphorylation of the IGF-I receptor was also inhibited as a function of DN concentration (10-100 mu M). However, DN at 200 mu M concentration had minimal effect on protein kinase C dependent phos phorylation. The IGF-I-dependent protein tyrosine phosphorylation of e ndogenous proteins of the rat spinal cord was also inhibited by 50 mu M DN. The altered IGF-I-dependent protein tyrosine phosphorylation by DN may partially explain its mechanism of action as an antitumor agent . These observations may also explain the neurotoxic effects of DN.