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Sci. Signal., 30 March 2010
Vol. 3, Issue 115, p. ra25
[DOI: 10.1126/scisignal.2000616]


New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion

Anna Zagórska1*{dagger}, Maria Deak1, David G. Campbell1, Sourav Banerjee1, Mariko Hirano2, Shinichi Aizawa2, Alan R. Prescott3, and Dario R. Alessi1{dagger}

1 MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.
2 Laboratory for Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Minami-machi, Chuo-ku, Kobe, Japan.
3 Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.

* Present address: Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA, USA.

Abstract: The AMPK-related kinases NUAK1 and NUAK2 are activated by the tumor suppressor LKB1. We found that NUAK1 interacts with several myosin phosphatases, including the myosin phosphatase targeting-1 (MYPT1)–protein phosphatase-1β (PP1β) complex, through conserved Gly-Ile-Leu-Lys motifs that are direct binding sites for PP1β. Phosphorylation of Ser445, Ser472, and Ser910 of MYPT1 by NUAK1 promoted the interaction of MYPT1 with 14-3-3 adaptor proteins, thereby suppressing phosphatase activity. Cell detachment induced phosphorylation of endogenous MYPT1 by NUAK1, resulting in 14-3-3 binding to MYPT1 and enhanced phosphorylation of myosin light chain-2. Inhibition of the LKB1-NUAK1 pathway impaired cell detachment. Our data indicate that NUAK1 controls cell adhesion and functions as a regulator of myosin phosphatase complexes. Thus, LKB1 can influence the phosphorylation of targets not only through the AMPK family of kinases but also by controlling phosphatase complexes.

{dagger} To whom correspondence should be addressed. E-mail: azagorska{at} (A.Z.); d.r.alessi{at} (D.R.A.)

Citation: A. Zagórska, M. Deak, D. G. Campbell, S. Banerjee, M. Hirano, S. Aizawa, A. R. Prescott, D. R. Alessi, New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion. Sci. Signal. 3, ra25 (2010).

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