Three-dimensional docking in the MAPK p38α.

Mitogen-activated protein kinases (MAPKs) are central players in eukaryotic signaling circuitry and interact with numerous other proteins. The structure of a MAPK with a kinase-binding domain (KBD) from a MAPK phosphatase, MKP5, reveals that the contacts with the MAPK are made with the folded three-dimensional KBD, although the KBD occupies the same binding site on the kinase as canonical linear docking motifs found in substrates and MAPK kinases. This structure offers insights into the action of MKP5 and other MKPs.