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 TS1 alpha beta 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 TS1 alpha beta 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 IL4-deprived cells correlates with inhibition of c-Jun N-terminal kinase 2 activity. Finally, TS1 alpha beta survival is independent of Bcl-2, Bcl-x, or Bax.