Metabolism, Cancer, and a Fuel Gauge

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Science  14 Nov 2003:
Vol. 302, Issue 5648, pp. 1117
DOI: 10.1126/science.302.5648.1117b

As a key sensor of cellular energy status, the AMP-activated protein kinase (AMPK) has attracted considerable attention among researchers studying metabolic control. In response to cellular stresses that deplete energy stores—such as glucose deprivation, hypoxia, and ischemia—AMPK is activated and switches on biosynthetic pathways that generate ATP while switching off pathways that consume ATP. The AMPK signaling cascade has been implicated in a range of human diseases, including type 2 diabetes, obesity, and cardiac hypertrophy.

Activation of AMPK requires phosphorylation of Thr172, but the upstream kinase(s) acting on AMPK have eluded detection. In independent studies, Hawley et al. and Woods et al. show that mammalian AMPK is phosphorylated by a protein complex containing LKB1, a serine/threonine kinase previously shown to function as a tumor suppressor protein. Mutations in the LKB1 gene cause Peutz-Jeghers syndrome, a human disorder associated with a 15-fold increased risk of developing cancer. This newly discovered link between two kinases once thought to lie in distinct signaling pathways provides an opportunity for studying the molecular mechanisms that underlie some of the most common human diseases. — PAK

J. Biol. 2, 28 (2003); Curr. Biol. 10.1016/S0960982203007851 (2003).

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