Selective Proteolysis to Study the Global Conformation and Regulatory Mechanisms of c-Src Kinase.
ACS Chem Biol
; 14(7): 1556-1563, 2019 07 19.
Article
en En
| MEDLINE
| ID: mdl-31287657
ABSTRACT
Protein kinase pathways are traditionally mapped by monitoring downstream phosphorylation. Meanwhile, the noncatalytic functions of protein kinases remain under-appreciated as critical components of kinase signaling. c-Src is a protein kinase known to have noncatalytic signaling function important in healthy and disease cell signaling. Large conformational changes in the regulatory domains regulate c-Src's noncatalytic functions. Herein, we demonstrate that changes in the global conformation of c-Src can be monitored using a selective proteolysis methodology. Further, we use this methodology to investigate changes in the global conformation of several clinical and nonclinical mutations of c-Src. Significantly, we identify a novel activating mutation observed clinically, W121R, that can escape down-regulation mechanisms. Our methodology can be expanded to monitor the global conformation of other tyrosine kinases, including c-Abl, and represents an important tool toward the elucidation of the noncatalytic functions of protein kinases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína Tirosina Quinasa CSK
Límite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos