Reference Report

Reference
Citation	Mirouse, V., Swick, L.L., Kazgan, N., St Johnston, D., Brenman, J.E. (2007). LKB1 and AMPK maintain epithelial cell polarity under energetic stress. J. Cell Biol. 177(3): 387--392. (Export to RIS)
FlyBase ID	FBrf0201625
Publication Type	Research paper
PubMed ID	17470638
PubMed 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.
DOI	10.1083/jcb.200702053
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Cell Biol.
Title	Journal of Cell Biology
Publication Year	1966-
ISBN/ISSN	0021-9525
Data from Reference
Aberrations (2)
	Df(1)AD11 Df(1)Exel6227
Alleles (16)
	Act5C^{Scer\UAS.T:Avic\GFP} CoVa^tend lkb1^4A4-2 lkb1^{Scer\UAS.P\T.T:Avic\GFP} Scer\GAL4^109(2)80 Scer\GAL4^CY2 Scer\GAL4^da.G32 Scer\GAL4^Ubi SNF1A¹ SNF1A² SNF1A³ SNF1A^Scer\UAS.cMa SNF1A^{Scer\UAS.T:Disc\RFP-mCherry} SNF1A^{T184D.Scer\UAS} T:Disc\RFP^mCherry w^+mC
Constructs (7)
	P{GAL4-da.G32} P{UAS-Act5C.T:GFP} P{UAS-mCherry-SNF1A} P{UASp-GFP-lkb1.wt} P{UAS-SNF1A.M} P{UAS-SNF1A.T184D} P{Ubi-GAL4}
Genes (13)
	Act5C aPKC baz cora CoVa crb Dg dlg1 lkb1 Scer\GAL4 shg SNF1A w
Insertions (2)
	P{GawB}109(2)80 P{GawB}CY2
Natural transposons (1)
	P-element