Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line.
Apoptosis (programmed cell death) plays a critical role in many physiological processes, but the mechanism(s) which regulate apoptosis are poorly understood. We demonstrate that in a hematopoietic cell line, which can grow in either interleukin (IL)-2 or IL-3, both of these growth factors can increase bcl-2 mRNA levels and prevent apoptosis normally seen following growth factor withdrawal. Herbimycin A, a protein tyrosine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regulate bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor withdrawal but also confers resistance to the effect of herbimycin A. We conclude that herbimycin A-sensitive protein tyrosine kinases are involved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of Bcl-2 since Bcl-2 can exert its growth survival effect even in the presence of herbimycin A.
Otani
H
H
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Erdos
M
M
Leonard
W J
WJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D018274:Electroporation; D015971:Gene Expression Regulation, Enzymologic; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D011809:Quinones / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D017077:Culture Media, Conditioned; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011809:Quinones; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases