BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
PLoS One
; 9(2): e87684, 2014.
Article
em En
| MEDLINE
| ID: mdl-24523872
ABSTRACT
Breast tumor kinase (BRK), also known as protein tyrosine kinase 6 (PTK6), is a non-receptor tyrosine kinase overexpressed in more that 60% of human breast carcinomas. The overexpression of BRK has been shown to sensitize mammary epithelial cells to mitogenic signaling and to promote cell proliferation and tumor formation. The molecular mechanisms of BRK have been unveiled by the identification and characterization of BRK target proteins. Downstream of tyrosine kinases 1 or Dok1 is a scaffolding protein and a substrate of several tyrosine kinases. Herein we show that BRK interacts with and phosphorylates Dok1 specifically on Y362. We demonstrate that this phosphorylation by BRK significantly downregulates Dok1 in a ubiquitin-proteasome-mediated mechanism. Together, these results suggest a novel mechanism of action of BRK in the promotion of tumor formation, which involves the targeting of tumor suppressor Dok1 for degradation through the ubiquitin proteasomal pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Proteínas Tirosina Quinases
/
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Proteínas de Ligação a RNA
/
Complexo de Endopeptidases do Proteassoma
/
Proteínas de Ligação a DNA
/
Proteínas de Neoplasias
Limite:
Female
/
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Canadá