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

RESEARCH ARTICLES

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).

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