Linked Life Data

11360179

Source:http://linkedlifedata.com/resource/pubmed/id/11360179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2001-5-21
pubmed:abstractText
We utilized a cDNA expression library derived from the B6SutA(1) mouse myeloid progenitor cell line to search for novel oncogenes that promote growth transformation of NIH3T3 cells. A 2.2 kb transforming cDNA was recovered that encodes the wild type thrombin-stimulated G protein-coupled receptor PAR-1. In addition to its potent focus forming activity, constitutive overexpression of PAR-1 in NIH3T3 cells promoted the loss of anchorage- and serum-dependent growth. Although inhibitors of thrombin failed to block PAR-1 transforming activity, a PAR-1 mutant that cannot be cleaved by thrombin was nontransforming. Since the foci of transformed cells induced by PAR-1 bear a striking resemblance to those induced by activated RhoA, we determined if PAR-1 transformation was due to the aberrant activation of a specific Rho family member. Like RhoA, PAR-1 cooperated with activated Raf-1 and caused synergistic enhancement of transforming activity, induced stress fibers when microinjected into porcine aortic endothelial cells, stimulated the activity of the serum response factor and NF-kappaB transcription factors, and PAR-1 transformation was blocked by co-expression of dominant negative RhoA. Finally, PAR-1 transforming activity was blocked by pertussis toxin and by co-expression of the RGS domain of Lsc, implicating Galpha(i) and Galpha(12)/Galpha(13) subunits, respectively, as mediators of PAR-1 transformation. Taken together, these observations suggest that PAR-1 growth transformation is mediated, in part, by activation of RhoA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1953-63
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11360179-3T3 Cells, pubmed-meshheading:11360179-Actins, pubmed-meshheading:11360179-Animals, pubmed-meshheading:11360179-Cell Adhesion, pubmed-meshheading:11360179-Cell Division, pubmed-meshheading:11360179-Cell Line, pubmed-meshheading:11360179-Cell Transformation, Neoplastic, pubmed-meshheading:11360179-DNA, Complementary, pubmed-meshheading:11360179-DNA-Binding Proteins, pubmed-meshheading:11360179-GTP-Binding Protein alpha Subunits, G12-G13, pubmed-meshheading:11360179-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:11360179-Mice, pubmed-meshheading:11360179-Myeloid Cells, pubmed-meshheading:11360179-Receptor, PAR-1, pubmed-meshheading:11360179-Receptors, Thrombin, pubmed-meshheading:11360179-Signal Transduction, pubmed-meshheading:11360179-Transfection, pubmed-meshheading:11360179-rho GTP-Binding Proteins, pubmed-meshheading:11360179-rhoA GTP-Binding Protein
pubmed:year
2001
pubmed:articleTitle
The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways.
pubmed:affiliation
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina NC 27599-7295, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't