Cleavage and relocation of the tyrosine kinase P59FYN during Fas-mediated apoptosis in T lymphocytes.
Ligation of Fas with its natural ligand or with anti-Fas antibodies induces an apoptotic program in Fas sensitive cells. We report here the identification of the tyrosine kinase p59Fyn as a substrate for CPP32-like proteinases and more particularly caspase 3 during Fas-mediated apoptosis in Jurkat T cells. Inhibition of CPP32-like proteinases by Ac-Asp-Glu-Val-Asp-aldehyde but not by Ac-Tyr-Val-Ala-Asp-aldehyde prevents CPP32, PARP and p59Fyn cleavage indicating that CPP32 or CPP32-like proteinases are responsible for the cleavage of p59Fyn. Cleavage occurs in the N-terminal domain of p59Fyn between Asp19 and Gly20 and is accompanied by relocation of an active p57Fyn kinase to cytoplasm of Fas-stimulated Jurkat cells as judged by both biochemical and confocal microscopy experiments. Thus, p59Fyn relocation and activity may play an important role during Fas-mediated cell death in human T lymphocytes.
Ricci
J E
JE
CJF 96.05 Activation des Cellules Hematopoietiques Faculté de Médecine, Nice, France.
Maulon
L
L
Luciano
F
F
Guerin
S
S
Livolsi
A
A
Mari
B
B
Breittmayer
J P
JP
Peyron
J F
JF
Auberger
P
P
D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002999:Clone Cells; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells; D019814:Myristic Acid / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology; D019014:fas Receptor / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019014:fas Receptor; D019814:Myristic Acid; D019308:Palmitic Acid; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases