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Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade

Simon A Hawley1, Jérôme Boudeau2, Jennifer L Reid1, Kirsty J Mustard1, Lina Udd3, Tomi P Mäkelä3, Dario R Alessi2* and D Grahame Hardie1*

Author Affiliations

1 Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK

2 MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK

3 Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland

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Journal of Biology 2003, 2:28  doi:10.1186/1475-4924-2-28

Correspondence regarding LKB1 should be addressed to Dario Alessi and regarding AMPK to Grahame Hardie.

Published: 24 September 2003

Additional files

Additional data file 1:

Alignment of the amino acid sequences of Tos3, Pak1 and Elm1 from Saccharomyces cerevisiae, and LKB1 and CaMKKβ (β3 variant) from humans. The alignment was created using PILEUP from the GCG suite [48] and the consensus sequence determined, and color added, using BOXSHADE 3.2.1 [49]. Residues that are identical in at least half of the sequences are colored red, with conservative changes in blue. The consensus sequence is represented by an upper case letter if the residue at a particular position is identical in all sequences, and by a lower case letter if at least half are conserved. Only the conserved central regions containing the kinase domains are shown (the kinase domain of LKB1 is approximately residues 44-309).

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Additional data file 2:

Sequence alignment of the activation loop sequences of AGC subfamily kinases (PKAα and PKCα, which are not thought to be activated by LKB1) with the activation loop residues of the AMPK/SNF1 subfamily of protein kinases. The methods used and color-coding are as in Additional data file 1. The threonine residues corresponding to Thr172 of AMPK ('P') and other residues mentioned in the text are indicated with downward arrows. All sequences are from humans, except AtSnRK1-α1, AtSnRK1-α1 and ScSnf1, which are the Arabidopsis thaliana (AtSnRK1, SNF1-related kinase-1) and Saccharomyces cerevisiae (ScSnf1) homologs of AMPK. Although the human, A. thaliana and S. cerevisiae homologs, as well as the PKAα and PKCα kinases, are known to be activated by phosphorylation of the threonine residue equivalent to Thr172, it has yet to be established whether the other AMPK subfamily members (NuaK1, NuaK2, BrsK1, BrsK2, SIK, QIK, QSK, MELK and PAR1A) are activated by phosphorylation at this residue, and whether LKB1:STRAD:MO25 complexes can mediate this phosphorylation.

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