Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt

TLDR

BAD, a pro‑apoptotic Bcl‑2 family protein, induces cell death unless phosphorylated, which inhibits its activity. IL‑3 stimulates PI3K‑dependent activation of Akt, which then phosphorylates BAD; this phosphorylation is blocked by PI3K inhibitors. Active Akt phosphorylates BAD at the IL‑3–responsive residues, showing that the PI3K‑Akt pathway regulates BAD’s pro‑apoptotic function.

Abstract

BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase–dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase–Akt pathway.