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)

    Research output: Contribution to journalArticle

    86 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

    Cite this

    Zagorska, Anna ; Deak, Maria ; Campbell, David G. ; Banerjee, Sourav ; Hirano, Mariko ; Aizawa, Shinichi ; Prescott, Alan R. ; Alessi, Dario R. / New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion. In: Science Signaling. 2010 ; Vol. 3, No. 115. pp. -.
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    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.",
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    New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion. / Zagorska, Anna (Lead / Corresponding author); Deak, Maria; Campbell, David G.; Banerjee, Sourav; Hirano, Mariko; Aizawa, Shinichi; Prescott, Alan R.; Alessi, Dario R. (Lead / Corresponding author).

    In: Science Signaling, Vol. 3, No. 115, ra25, 30.03.2010, p. -.

    Research output: Contribution to journalArticle

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    AU - Deak, Maria

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    AU - Banerjee, Sourav

    AU - Hirano, Mariko

    AU - Aizawa, Shinichi

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