Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.
Mol Cell
; 53(1): 140-7, 2014 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-24374310
ABSTRACT
Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proteínas Serina-Treonina Quinases
/
Quinases Ativadas por p21
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Cell
Ano de publicação:
2014
Tipo de documento:
Article