Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation.
We have shown previously that interleukin-4 (IL-4) protects TS1alphabeta cells from apoptosis, but very little is known about the mechanism by which IL-4 exerts this effect. We found that Akt activity, which is dependent on phosphatidylinositol 3 kinase, is reduced in IL-4-deprived TS1alphabeta cells. Overexpression of wild-type Akt or a constitutively active Akt mutant protects cells from IL-4 deprivation-induced apoptosis. Readdition of IL-4 before the commitment point is able to restore Akt activity. We also show expression and c-Jun N-terminal kinase 2 activation after IL-4 deprivation. Overexpression of the constitutively activated Akt mutant in IL-4-deprived cells correlates with inhibition of c-Jun N-terminal kinase 2 activity. Finally, TS1alphabeta survival is independent of Bcl-2, Bcl-x, or Bax.
Cerezo
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Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autónoma, Campus de Cantoblanco, E-28049 Madrid, Spain.
Martínez-A
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C
Lanzarot
D
D
Fischer
S
S
Franke
T F
TF
Rebollo
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D000818:Animals; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D015847:Interleukin-4 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015854:Up-Regulation
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015847:Interleukin-4; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt