Optical control of cell signaling by single-chain photoswitchable kinases.
Science
; 355(6327): 836-842, 2017 02 24.
Article
em En
| MEDLINE
| ID: mdl-28232577
ABSTRACT
Protein kinases transduce signals to regulate a wide array of cellular functions in eukaryotes. A generalizable method for optical control of kinases would enable fine spatiotemporal interrogation or manipulation of these various functions. We report the design and application of single-chain cofactor-free kinases with photoswitchable activity. We engineered a dimeric protein, pdDronpa, that dissociates in cyan light and reassociates in violet light. Attaching two pdDronpa domains at rationally selected locations in the kinase domain, we created the photoswitchable kinases psRaf1, psMEK1, psMEK2, and psCDK5. Using these photoswitchable kinases, we established an all-optical cell-based assay for screening inhibitors, uncovered a direct and rapid inhibitory feedback loop from ERK to MEK1, and mediated developmental changes and synaptic vesicle transport in vivo using light.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MAP Quinase Quinase 1
/
MAP Quinases Reguladas por Sinal Extracelular
/
Inibidores de Proteínas Quinases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos