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Rockefeller University Press, Journal of Cell Biology, 2(203), p. 373-373, 2013

DOI: 10.1083/jcb.20070205310112013r

Rockefeller University Press, Journal of Cell Biology, 3(177), p. 387-392, 2007

DOI: 10.1083/jcb.200702053

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LKB1 and AMPK maintain epithelial cell polarity under energetic stress

Journal article published in 2007 by Vincent Mirouse, Lance L. Swick, Nevzat Kazgan, Daniel St Johnston ORCID, Jay E. Brenman
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5'monophosphate-activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1-AMPK signaling in vertebrates has been complicated by the existence of multiple redundant AMPK subunits. We describe the identification of mutations in the single Drosophila melanogaster AMPK catalytic subunit AMPKalpha. Surprisingly, ampkalpha mutant epithelial cells lose their polarity and overproliferate under energetic stress. LKB1 is required in vivo for AMPK activation, and lkb1 mutations cause similar energetic stress-dependent phenotypes to ampkalpha mutations. Furthermore, lkb1 phenotypes are rescued by a phosphomimetic version of AMPKalpha. Thus, LKB1 signals through AMPK to coordinate epithelial polarity and proliferation with cellular energy status, and this might underlie the tumor suppressor function of LKB1.