A G1 cell cycle arrest induced by ligands of the reovirus type 3 receptor is secondary to inactivation of p21ras and mitogen-activated protein kinase.
DNA Cell Biol
; 18(10): 763-70, 1999 Oct.
Article
em En
| MEDLINE
| ID: mdl-10541435
ABSTRACT
The reovirus type 3 S1 gene product (type 3 hemagglutinin; HA3) is the viral protein responsible for binding to a mammalian cell-surface receptor. It has been shown that HA3 binding to its receptor inhibits cell growth, even in the continuous presence of serum mitogens. Here, receptor-mediated signal transduction leading to growth arrest was studied after binding with synthetic or recombinant ligands in the absence of viral infection. Receptor ligation caused rapid inactivation of p21(ras), a decrease in Raf phosphorylation and in mitogen-activated protein kinase (MAPK) enzymatic activity, and G1 cell cycle arrest. Transfection and expression of constitutively active v-Has-ras prevented the G1 arrest, indicating that inactivation of p21(ras) is causative. Interestingly, v-Has-ras expression also decreased the efficiency of reoviridae replication, suggesting that inactivation of p21(ras) signals is required at some step of the viral cycle. This study may define new mechanisms regulating cell growth and support the approach of using viral proteins to identify and study cellular receptors. Synthetic receptor ligands with antiproliferative properties may be useful in drug development with the aim of blocking mitosis.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Receptores Virais
/
Orthoreovirus Mamífero 3
/
Proteínas Virais
/
Proteína Oncogênica p21(ras)
/
Fase G1
/
Proteínas Proto-Oncogênicas p21(ras)
/
Proteínas de Ciclo Celular
/
Proteínas Quinases Ativadas por Mitógeno
/
Sistema de Sinalização das MAP Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
DNA Cell Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Canadá