Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

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

RESEARCH ARTICLES

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}salk.edu (A.Z.); d.r.alessi{at}dundee.ac.uk (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).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Tumor Suppressor Kinase LKB1 Activates the Downstream Kinases SIK2 and SIK3 to Stimulate Nuclear Export of Class IIa Histone Deacetylases.
D. R. Walkinshaw, R. Weist, G.-W. Kim, L. You, L. Xiao, J. Nie, C. S. Li, S. Zhao, M. Xu, and X.-J. Yang (2013)
J. Biol. Chem. 288, 9345-9362
   Abstract »    Full Text »    PDF »
Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility.
T. Butler, J. Paul, N. Europe-Finner, R. Smith, and E.-C. Chan (2013)
Am J Physiol Cell Physiol 304, C485-C504
   Abstract »    Full Text »    PDF »
Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways.
B. Lo, G. Strasser, M. Sagolla, C. D. Austin, M. Junttila, and I. Mellman (2012)
J. Cell Biol. 199, 1117-1130
   Abstract »    Full Text »    PDF »
Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis.
A. E. Rodriguez-Fraticelli, M. Auzan, M. A. Alonso, M. Bornens, and F. Martin-Belmonte (2012)
J. Cell Biol. 198, 1011-1023
   Abstract »    Full Text »    PDF »
LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression.
T. Chiyoda, N. Sugiyama, T. Shimizu, H. Naoe, Y. Kobayashi, J. Ishizawa, Y. Arima, H. Tsuda, M. Ito, K. Kaibuchi, et al. (2012)
J. Cell Biol. 197, 625-641
   Abstract »    Full Text »    PDF »
Muscle-specific Knock-out of NUAK Family SNF1-like Kinase 1 (NUAK1) Prevents High Fat Diet-induced Glucose Intolerance.
F. Inazuka, N. Sugiyama, M. Tomita, T. Abe, G. Shioi, and H. Esumi (2012)
J. Biol. Chem. 287, 16379-16389
   Abstract »    Full Text »    PDF »
Actin stress fibers - assembly, dynamics and biological roles.
S. Tojkander, G. Gateva, and P. Lappalainen (2012)
J. Cell Sci. 125, 1855-1864
   Abstract »    Full Text »    PDF »
The tumor suppressor kinase LKB1: lessons from mouse models.
S. Ollila and T. P. Makela (2011)
J Mol Cell Biol 3, 330-340
   Abstract »    Full Text »    PDF »
Myosin Phosphatase-targeting Subunit 1 Controls Chromatid Segregation.
F. Matsumura, Y. Yamakita, and S. Yamashiro (2011)
J. Biol. Chem. 286, 10825-10833
   Abstract »    Full Text »    PDF »
An association between NUAK2 and MRIP reveals a novel mechanism for regulation of actin stress fibers.
T. Vallenius, K. Vaahtomeri, B. Kovac, A.-M. Osiceanu, M. Viljanen, and T. P. Makela (2011)
J. Cell Sci. 124, 384-393
   Abstract »    Full Text »    PDF »
Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway.
D. Fu, Y. Wakabayashi, J. Lippincott-Schwartz, and I. M. Arias (2011)
PNAS 108, 1403-1408
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 30 March 2010.
D. R. Alessi and A. M. VanHook (2010)
Science Signaling 3, pc7
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882