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

Anna Zagorska (Lead / Corresponding author), Maria Deak, David G. Campbell, Sourav Banerjee, Mariko Hirano, Shinichi Aizawa, Alan R. Prescott, Dario R. Alessi (Lead / Corresponding author)

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100 Citations (Scopus)

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-1 beta (PP1 beta) complex, through conserved Gly-Ile-Leu-Lys motifs that are direct binding sites for PP1b. Phosphorylation of Ser(445), Ser(472), and Ser(910) 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.

Original languageEnglish
Article numberra25
Pages (from-to)-
Number of pages13
JournalScience Signaling
Volume3
Issue number115
DOIs
Publication statusPublished - 30 Mar 2010

Keywords

  • ACTIVATED PROTEIN-KINASE
  • STRUCTURAL BASIS
  • REGULATORY SUBUNITS
  • SIGNALING PATHWAYS
  • CATALYTIC SUBUNIT
  • SKELETAL-MUSCLE
  • HUMAN CANCER
  • LKB1
  • AMPK
  • SUBSTRATE

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