A Bad kinase makes good

The Bcl-2 family of proteins has been implicated in cell survival decisions. Bcl-2 and Bcl-x_Lsuppress apoptosis, in part by blocking the release of cytochrome c from mitochondria, a critical step in the activation of the caspase protease cascade. Other family members, such as Bad and Bax, interfere with the activity of Bcl-2 or Bcl-x_L by binding to them and forming non-functional heterodimers⁴. In response to interleukin-3, for example, Bad is phosphorylated at two sites, dissociates from Bcl-x_Land then interacts with the phosphoserine-binding protein, 14-3-3 (ref. 5). The released Bcl-x_Lthen promotes cell survival by blocking the caspase protease cascade.

Del Peso et al.² now show that PI3K activity is necessary for the phosphorylation of Bad after interleukin-3 treatment of cells. Moreover, they have identified Akt as the kinase that phosphorylates Bad on a site that is required for its interaction with 14-3-3. Datta and colleagues³ independently identified Bad as a substrate for the Akt kinase and showed that of two potential phosphorylation sites in mouse Bad, only one (Ser 136) is phosphorylated by Akt. Furthermore, they demonstrate that Akt overexpression prevents Bad-induced cell death of cerebellar granule neurons, suggesting that Akt-dependent cell survival is mediated in part by phosphorylation of Bad.