A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation

Xin Liu; Chen-Song Zhang; Chang Lu; Sheng-Cai Lin; Jia-Wei Wu; Zhi-Xin Wang

doi:10.1038/ncomms10879

A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation

Nat Commun. 2016 Mar 18:7:10879. doi: 10.1038/ncomms10879.

Authors

Xin Liu¹, Chen-Song Zhang², Chang Lu¹, Sheng-Cai Lin², Jia-Wei Wu¹, Zhi-Xin Wang¹

Affiliations

¹ Key Laboratory of Ministry of Education for Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
² State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.

Abstract

Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs). MAPK signalling efficiency and specificity is modulated by protein-protein interactions between individual MAPKs and the docking motifs in cognate binding partners. Two types of docking interactions have been identified: D-motif-mediated interaction and FXF-docking interaction. Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction. The (285)FNFL(288) segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs
Amino Acid Sequence
Apoptosis / radiation effects
Biocatalysis
Catalytic Domain
Conserved Sequence*
Crystallography, X-Ray
DNA Mutational Analysis
Dual-Specificity Phosphatases / chemistry*
Dual-Specificity Phosphatases / metabolism*
Enzyme Activation
HEK293 Cells
HeLa Cells
Humans
Mitogen-Activated Protein Kinase 8 / chemistry
Mitogen-Activated Protein Kinase 8 / metabolism*
Mitogen-Activated Protein Kinase Phosphatases / chemistry*
Mitogen-Activated Protein Kinase Phosphatases / metabolism*
Molecular Docking Simulation
Molecular Sequence Data
Phosphorylation
Protein Binding
Structure-Activity Relationship
Substrate Specificity
Ultraviolet Rays
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Mitogen-Activated Protein Kinase 8
p38 Mitogen-Activated Protein Kinases
DUSP10 protein, human
Mitogen-Activated Protein Kinase Phosphatases
DUSP16 protein, human
Dual-Specificity Phosphatases