Editors' ChoiceApoptosis

ASKing for Akt

Science's STKE  23 Jan 2001:
Vol. 2001, Issue 66, pp. tw9
DOI: 10.1126/stke.2001.66.tw9

One way that the serine/threonine kinase Akt (protein kinase B) could regulate cell survival would be to suppress proapoptotic signaling pathways. Indeed, Kim et al. suggest just that. Biochemical analysis of a mitogen-activated protein kinase kinase kinase called apoptosis signal-regulated kinase 1 (ASK1) revealed that it is a substrate of Akt. When phosphorylated by Akt, ASK1 could no longer activate the c-Jun NH2-terminal kinase (JNK) signaling pathway, which is implicated in stress-induced apoptosis. Akt and ASK1 appear to directly interact, and the phosphorylation site was mapped to the amino terminal regulatory domain of ASK1. The ability of ASK1 to induce apoptosis in cultured cells was also diminished when the phosphoinositide 3-kinase/Akt pathway was activated by growth factor treatment. Hence, Akt appears to suppress ASK1-induced cell killing.

A. J. Kim, G. Khursigara, X. Sun, T. F. Franke, M. V. Chao, Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol. Cell Biol. 21, 893-901 (2001). [Abstract] [Full Text]