Co-conserved MAPK features couple D-domain docking groove to distal allosteric sites via the C-terminal flanking tail.

ABSTRACT: Mitogen activated protein kinases (MAPKs) form a closely related family of kinases that control critical pathways associated with cell growth and survival. Although MAPKs have been extensively characterized at the biochemical, cellular, and structural level, an integrated evolutionary understanding of how MAPKs differ from other closely related protein kinases is currently lacking. Here, we perform statistical sequence comparisons of MAPKs and related protein kinases to identify sequence and structural features associated with MAPK functional divergence. We show, for the first time, that virtually all MAPK-distinguishing sequence features, including an unappreciated short insert segment in the β4-β5 loop, physically couple distal functional sites in the kinase domain to the D-domain peptid

SUBMITTER: Nguyen T 

PROVIDER: S-EPMC4370755 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature