A G[sub 1] Cell Cycle Arrest Induced by Ligands of the Reovirus Type 3 Receptor Is Secondary to Inactivation of p21ras and Mitogen-Activated Protein Kinase

Saragovi, H. Uri; Rebai, Najet; Guglielmo, Gianni M. Di; MaCleod, Robert; Sheng, Jinsong; Rubin, Donald H.; Greene, Mark I.
October 1999
DNA & Cell Biology;Oct99, Vol. 18 Issue 10, p763
Academic Journal
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 p21ras, a decrease in Raf phosphorylation and in mitogenactivated protein kinase (MAPK) enzymatic activity, and G[sub 1] cell cycle arrest. Transfection and expression of constitutively active v-Has-ras prevented the G[sub 1] arrest, indicating that inactivation of p21ras is causative. Interestingly, v-Has-ras expression also decreased the efficiency of reoviridae replication, suggesting that inactivation of p21ras 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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