Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-11-22
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Capsid Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Diphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/HRAS protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Virus, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins, http://linkedlifedata.com/resource/pubmed/chemical/reovirus type 3 receptor, http://linkedlifedata.com/resource/pubmed/chemical/sigma 1 protein, reovirus
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
763-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10541435-Animals, pubmed-meshheading:10541435-Antibodies, Monoclonal, pubmed-meshheading:10541435-Capsid Proteins, pubmed-meshheading:10541435-Cell Cycle Proteins, pubmed-meshheading:10541435-Cell Division, pubmed-meshheading:10541435-Cytopathogenic Effect, Viral, pubmed-meshheading:10541435-G1 Phase, pubmed-meshheading:10541435-Genes, ras, pubmed-meshheading:10541435-Growth Inhibitors, pubmed-meshheading:10541435-Guanosine Diphosphate, pubmed-meshheading:10541435-Guanosine Triphosphate, pubmed-meshheading:10541435-Humans, pubmed-meshheading:10541435-Ligands, pubmed-meshheading:10541435-MAP Kinase Signaling System, pubmed-meshheading:10541435-Mammalian orthoreovirus 3, pubmed-meshheading:10541435-Mice, pubmed-meshheading:10541435-Mitogen-Activated Protein Kinases, pubmed-meshheading:10541435-Oncogene Protein p21(ras), pubmed-meshheading:10541435-Peptides, Cyclic, pubmed-meshheading:10541435-Phosphorylation, pubmed-meshheading:10541435-Protein Processing, Post-Translational, pubmed-meshheading:10541435-Protein Structure, Tertiary, pubmed-meshheading:10541435-Proto-Oncogene Proteins c-raf, pubmed-meshheading:10541435-Proto-Oncogene Proteins p21(ras), pubmed-meshheading:10541435-Receptors, Virus, pubmed-meshheading:10541435-Recombinant Fusion Proteins, pubmed-meshheading:10541435-Transfection, pubmed-meshheading:10541435-Tumor Cells, Cultured, pubmed-meshheading:10541435-Viral Proteins, pubmed-meshheading:10541435-Virus Replication
pubmed:year
1999
pubmed:articleTitle
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.
pubmed:affiliation
Department of Pharmacology, McGill Cancer Center, McGill University, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't