Inhibition of tyrosine protein kinases by the antineoplastic agent adriamycin.
Adriamycin, a lipid-interacting anti-cancer agent, was found to inhibit the phosphorylation of polyGlu/Tyr (4:1) by tyrosine protein kinases either from spleen or expressed by the oncogene of Abelson murine leukemia virus. The dose dependent inhibition by adriamycin is accounted for by competition for the ATP binding site, but it is also deeply influenced by the nature and concentration of the phosphorylatable substrate, suggesting multiple interactions with the enzyme. The phosphorylation at tyrosine residues of cytosolic proteins from cells transformed by Abelson leukemia virus and the autophosphorylation of tyrosine protein kinases are also inhibited by adriamycin. Unlike tyrosine protein kinases most serine/threonine specific protein kinases, with the notable exception of protein kinase-C, appear to be relatively insensitive to adriamycin.
Donella-Deana
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Dipartimento di Chimica Biologica dell'Universita' di Padova, Italy.
Monti
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Pinna
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LA
D000011:Abelson murine leukemia virus / Q000201:enzymology / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D047388:Casein Kinases; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D011558:Herpesvirus 1, Suid / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D009857:Oncogenes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D013154:Spleen / Q000201:enzymology; D013552:Swine
D047428:Protein Kinase Inhibitors; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D047388:Casein Kinases; D011493:Protein Kinase C