A conserved salt bridge in the G loop of multiple protein kinases is important for catalysis and for in vivo Lyn function.
Mol Cell
; 33(1): 43-52, 2009 Jan 16.
Article
en En
| MEDLINE
| ID: mdl-19150426
ABSTRACT
The glycine-rich G loop controls ATP binding and phosphate transfer in protein kinases. Here we show that the functions of Src family and Abl protein tyrosine kinases require an electrostatic interaction between oppositely charged amino acids within their G loops that is conserved in multiple other phylogenetically distinct protein kinases, from plants to humans. By limiting G loop flexibility, it controls ATP binding, catalysis, and inhibition by ATP-competitive compounds such as Imatinib. In WeeB mice, mutational disruption of the interaction results in expression of a Lyn protein with reduced catalytic activity, and in perturbed B cell receptor signaling. Like Lyn(-/-) mice, WeeB mice show profound defects in B cell development and function and succumb to autoimmune glomerulonephritis. This demonstrates the physiological importance of the conserved G loop salt bridge and at the same time distinguishes the in vivo requirement for the Lyn kinase activity from other potential functions of the protein.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Secuencia Conservada
/
Familia-src Quinasas
/
Electricidad Estática
/
Biocatálisis
Límite:
Animals
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos