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

被引：142

作者：

Zagorska, Anna ^{[1
]}

Deak, Maria ^{[1
]}

Campbell, David G. ^{[1
]}

Banerjee, Sourav ^{[1
]}

Hirano, Mariko ^{[2
]}

Aizawa, Shinichi ^{[2
]}

Prescott, Alan R. ^{[3
]}

Alessi, Dario R. ^{[1
]}

机构：

[1] Univ Dundee, MRC Prot Phosphorylat Unit, Coll Life Sci, Dundee DD1 5EH, Scotland

[2] RIKEN Kobe, Lab Vertebrate Body Plan, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo, Japan

[3] Univ Dundee, Div Cell Biol & Immunol, Coll Life Sci, Dundee DD1 5EH, Scotland

来源：

SCIENCE SIGNALING | 2010年 / 3卷 / 115期

基金：

英国医学研究理事会;

关键词：

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

D O I：

10.1126/scisignal.2000616

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

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