title: Daunomycin inhibits insulin-like growth factor I-dependent protein tyrosine phosphorylation.
abstract: The effect of the antitumor antibiotic daunomycin (DN) was studied on insulin-like growth factor I (IGF-I)-dependent protein tyrosine phosphorylation. DN was found to inhibit IGF-I-dependent phosphorylation of the artificial substrate poly(Glu:Tyr)4:1 by intrinsic IGF-I receptor kinase either from mouse cerebellum or from rat spinal cord. IGF-I-dependent autophosphorylation of the IGF-I receptor was also inhibited as a function of DN concentration (10-100 microM). However, DN at 200 microM concentration had minimal effect on protein kinase C dependent phosphorylation. The IGF-I-dependent protein tyrosine phosphorylation of endogenous proteins of the rat spinal cord was also inhibited by 50 microM 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.
authors.affiliation: Department of Neurology, University of Mississippi Medical Center, Jackson 39216, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Vig
authors.forename: D
authors.initials: D
authors.lastname: Desaiah
authors.forename: S H
authors.initials: SH
authors.lastname: Subramony
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology* / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D003630:Daunorubicin