Cell Survival

Signaling Survival Strategies

Science Signaling  06 May 2008:
Vol. 1, Issue 18, pp. ec170
DOI: 10.1126/stke.118ec170

Along with its role in control of metabolism, the enzyme glycogen synthase kinase 3β (GSK3β) functions in a signaling mechanism that controls transcription. When GSK3β is active, it phosphorylates β-catenin and promotes degradation of the β-catenin protein. Inhibition of GSK3 permits accumulation of β-catenin, which works in the nucleus with transcription factors to promote expression of target genes. Thornton et al. show that activation of the p38 mitogen-activated protein kinase (MAPK) appears to directly phosphorylate and thereby inhibit GSK3β. Mouse embryo fibroblasts lacking enzymes that lead to activation of p38 were deficient in phosphorylation of GSK3β. The authors propose that such a signaling pathway may allow cellular stresses and cytokines that activate p38 MAPK to influence cell survival.

T. M. Thornton, G. Pedraza-Alva, B. Deng, C. D. Wood, A. Aronshtam, J. L. Clements, G. Sabio, R. J. Davis, D. E. Matthews, B. Doble, M. Rincon, Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation. Science 320, 667-670 (2008). [Abstract] [Full Text]