Inhibition of pp60c-src protein kinase by herbimycin A in polyomavirus middle tumor antigen-transformed cells.
The middle T antigen (MTAg) encoded by polyomavirus plays an important role in virus-mediated tumorigenesis. The activated protein kinase activity of MTAg-associated pp60c-src has been shown to be necessary for cell transformation by polyomavirus. In this study, the effects of herbimycin A on the pp60c-src kinase activities in the polyomavirus- and MTAg-transformed cells were studied. Phosphorylation of src and MTAg is reduced in polyomavirus and MTAg- transformed cells pretreated with herbimycin A. Inactivation of the enzymatic activity by herbimycin A was found to be dependent on the time of incubation and the drug concentration. In contrast, src immunoprecipitates from untreated MTAg-transformed cells appeared to be resistant to inhibition by herbimycin A. Herbimycin A does not affect the synthesis of MTAg and pp60c-src in the MTAg-transformed cells. These results suggest that pp60c-src kinase activity in the drug-treated cell lysates is more sensitive to herbimycin A inhibition than the same activity in the immunoprecipitates.
Yang
Y W
YW
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chang
Y H
YH
D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000952:Antigens, Polyomavirus Transforming; D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D051379:Mice; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives
D000903:Antibiotics, Antineoplastic; D000952:Antigens, Polyomavirus Transforming; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D016392:Proto-Oncogene Proteins pp60(c-src)