FIGURE 1.

A PB1 domain in a MAPK kinase is unique to the ERK5 signaling module. A, the cladogram for MAPKs and their specific MKK activators. Cladograms were calculated based on the sequences of kinase domains for MAPKs or MKKs found in KinBase (57). CDK, cyclin-dependent kinase. (Atypical MAPKs are ERK3/4/7 or NLK (58), STE11 family is comprised of MAPK kinase kinases.). B, schematic organization of the MEKK2/3-MKK5-ERK5 MAPK module. PB1 domains from MEKK3 and MKK5 are shown with colored squares, and a box next to the ERK5 kinase domain indicates the long non-catalytic C-terminal tail (407–816) of ERK5. C, all MKKs contain a linear D-motif: their sequences are shown for the seven human MKKs. In the MKK D-motif consensus Ψ, Φ, and X denotes basic, hydrophobic, and any amino acids, respectively. In addition, MKK5 also contains an evolutionary conserved PB1 globular domain. The panel on the right shows the MAPK docking surface colored according to its electrostatic potential (positive in blue and negative in red) from the ERK2 crystal structure complexed with a peptide containing the MKK2 linear D-motif (shown in black with the side chains of the consensus motif forming amino acids indicated) (26).