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.


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


Editor's Summary

An LKB1 Pathway for Cell Adhesion
The tumor suppressor LKB1 is a serine-threonine kinase that phosphorylates and activates a family of structurally related kinases, the best studied of which is AMPK (adenosine monophosphate–activated protein kinase). A role for LKB1 and AMPK in the control of metabolism has been firmly established, and several downstream targets in the LKB1-AMPK pathway have been characterized. In contrast, the functions and targets of other AMPK-related kinases are not as well defined. For example, the AMPK-related kinase NUAK1 has been linked to tumor invasion, but the underlying mechanisms are unknown. Zagórska et al. performed a proteomic screen that revealed associations between NUAK1 and protein phosphatase 1β (PP1β) and three of its regulatory subunits, including MYPT1. The PP1β-MYPT1 complex regulates the phosphorylation of various proteins involved in cytoskeletal organization, such as myosin light chain-2, a regulatory subunit of the motor protein myosin. Phosphorylation of multiple residues in MYPT1 by NUAK1 recruited 14-3-3 proteins to MYPT1, an interaction that decreased the phosphatase activity of PP1β. Cell detachment was associated with a NUAK1-mediated reduction in the activity of the PP1β-MYPT1 complex and increased phosphorylation of myosin light chain-2, and loss of NUAK1 activity blocked cell detachment. Together, these results define a new function for LKB1 in decreasing cell adhesion through inhibition of myosin phosphatase activity and indicate that NUAK1 may contribute to tumor invasion by activating cytoskeletal motor proteins and thereby promoting cell detachment.

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

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 »
MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases.
B. M. Filippi, P. de los Heros, Y. Mehellou, I. Navratilova, R. Gourlay, M. Deak, L. Plater, R. Toth, E. Zeqiraj, and D. R. Alessi (2011)
EMBO J. 30, 1730-1741
   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