Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites.

ABSTRACT: Protein kinase autophosphorylation of activation segment residues is a common regulatory mechanism in phosphorylation-dependent signalling cascades. However, the molecular mechanisms that guarantee specific and efficient phosphorylation of these sites have not been elucidated. Here, we report on three novel and diverse protein kinase structures that reveal an exchanged activation segment conformation. This dimeric arrangement results in an active kinase conformation in trans, with activation segment phosphorylation sites in close proximity to the active site of the interacting protomer. Analytical ultracentrifugation and chemical cross-linking confirmed the presence of dimers in solution. Consensus substrate sequences for each kinase showed that the identified activation segment autophosph

SUBMITTER: Pike AC 

PROVIDER: S-EPMC2239268 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature