Structural snapshots of RAF kinase interactions.
Biochem Soc Trans
; 46(6): 1393-1406, 2018 12 17.
Article
em En
| MEDLINE
| ID: mdl-30381334
ABSTRACT
RAF (rapidly accelerated fibrosarcoma) Ser/Thr kinases (ARAF, BRAF, and CRAF) link the RAS (rat sarcoma) protein family with the MAPK (mitogen-activated protein kinase) pathway and control cell growth, differentiation, development, aging, and tumorigenesis. Their activity is specifically modulated by protein-protein interactions, post-translational modifications, and conformational changes in specific spatiotemporal patterns via various upstream regulators, including the kinases, phosphatase, GTPases, and scaffold and modulator proteins. Dephosphorylation of Ser-259 (CRAF numbering) and dissociation of 14-3-3 release the RAF regulatory domains RAS-binding domain and cysteine-rich domain for interaction with RAS-GTP and membrane lipids. This, in turn, results in RAF phosphorylation at Ser-621 and 14-3-3 reassociation, followed by its dimerization and ultimately substrate binding and phosphorylation. This review focuses on structural understanding of how distinct binding partners trigger a cascade of molecular events that induces RAF kinase activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-raf
/
Proteínas Quinases Ativadas por Mitógeno
/
Proteínas Proto-Oncogênicas B-raf
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Proteínas Proto-Oncogênicas A-raf
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Soc Trans
Ano de publicação:
2018
Tipo de documento:
Article