Dual specificity protein phosphatase 10
MAP kinase phosphatase activity
A distinct interaction mode revealed by the crystal structure of the kinase p38α with the MAPK binding domain of the phosphatase MKP5.
The mitogen-activated protein kinase (MAPK) cascades play a pivotal role in a                    myriad of cellular functions. The specificity and efficiency of MAPK signaling                    are controlled by docking interactions between MAPKs and their cognate proteins.                    Many MAPK-interacting partners, including substrates, MAPK kinases,                    phosphatases, and scaffolding proteins, have linear sequence motifs that mediate                    the interaction with the common docking site on MAPKs. We report the crystal                    structure of p38α in complex with the MAPK binding domain (KBD) from MAPK                    phosphatase 5 (MKP5) at 2.7 Å resolution. In contrast to the well-known                    docking mode, the KBD binds p38α in a bipartite manner, in which two                    distinct helical regions of KBD engage the p38α docking site, which is                    situated on the back of the p38α active site. We also determined the                    crystal structure of the KBD of MKP7, which closely resembles the MKP5 KBD,                    suggesting that the mechanism of molecular recognition by the KBD of MKP5 is                    conserved in the cytoplasmic p38- and c-Jun N-terminal kinase-specific                    MKP subgroup. This previously unknown binding mode provides new insights into                    how MAPKs interact with their binding partners to achieve functional                    specificity.