Regulation of apoptosis of interleukin 2-dependent mouse T-cell line by protein tyrosine phosphorylation and polyamines.
We examined the effect of inhibitors of tyrosine kinase and tyrosine phosphatase on DNA fragmentation, protein tyrosine phosphorylation, and polyamine metabolism in the murine T-cell line CTLL-2. When cells were exposed to herbimycin A, a specific inhibitor of tyrosine kinase (Uehara et al., 1989, Biochem. Biophys. Res. Commun., 163:803-809), in the presence of interleukin 2 (IL-2), DNA was degraded into oligonucleosomal fragments in a dose-dependent fashion. Genistein, another inhibitor of tyrosine kinase (Akiyama et al., 1987, J. Biol. Chem., 262:5592-5596), had similar effects. Exposure of CTLL-2 cells to vanadate, a tyrosine phosphatase inhibitor, blocked with the DNA fragmentation induced by herbimycin A. Tyrosine phosphorylation of 55 Kd protein was inhibited by herbimycin A, and the inhibition was reduced by vanadate. Ornithine decarboxylase (ODC) activity decreased rapidly after herbimycin A was added to CTLL-2 cell cultures, while vanadate increased ODC activity. The exogenous addition of putrescine or spermine, but not that of spermidine, attenuated herbimycin A-induced DNA fragmentation. These findings suggest that phosphorylation of tyrosine residues of 55 Kd protein prevents DNA fragmentation and that polyamines are involved in regulation of apoptosis.
Min
A
A
Department of Biochemistry, Osaka City University Medical School, Japan.
Hasuma
T
T
Yano
Y
Y
Matsui-Yuasa
I
I
Otani
S
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016227:Benzoquinones; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D047029:Lactams, Macrocyclic; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010766:Phosphorylation; D011073:Polyamines / Q000494:pharmacology*; D011419:Propidium; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D016227:Benzoquinones; D002843:Chromatin; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D047029:Lactams, Macrocyclic; D011073:Polyamines; D011809:Quinones; D017828:Rifabutin; D011419:Propidium; D014638:Vanadates; D014443:Tyrosine; C020754:herbimycin; D004247:DNA; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D009955:Ornithine Decarboxylase