The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module.

ABSTRACT: The catalytic activities of eukaryotic protein kinases (EPKs) are regulated by movement of the C-helix, movement of the N and C lobes upon ATP binding, and movement of the activation loop upon phosphorylation. Statistical analysis of the selective constraints associated with AGC kinase functional divergence reveals conserved interactions between these regulatory regions and three regions of the C-terminal tail (C-tail): the N-lobe tether (NLT), the active-site tether (AST), and the C-lobe tether (CLT). The NLT serves as a docking site for an upstream kinase PDK1 and, upon activation, positions the C-helix within the ATP binding pocket. The AST directly interacts with the ATP binding pocket, and the CLT interacts with the interlobe linker and the alphaC-beta4 loop, which appears to serve as

SUBMITTER: Kannan N 

PROVIDER: S-EPMC1783090 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature