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

作者：Zagorska Anna^*; Deak Maria; Campbell David G; Banerjee Sourav; Hirano Mariko; Aizawa Shinichi; Prescott Alan R; Alessi Dario R

来源：Science Signaling, 2010, 3(115): ra25.

DOI：10.1126/scisignal.2000616

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.

• 出版日期2010-3-30