Linked Life Data

15220352

Source:http://linkedlifedata.com/resource/pubmed/id/15220352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2004-9-6
pubmed:abstractText
Thy-1, a cell adhesion molecule abundantly expressed in mammalian neurons, binds to a beta(3)-containing integrin on astrocytes and thereby stimulates the assembly of focal adhesions and stress fibers. Such events lead to morphological changes in astrocytes that resemble those occurring upon injury in the brain. Extracellular matrix proteins, typical integrin ligands, bind to integrins and promote receptor clustering as well as signal transduction events that involve small G proteins and cytoskeletal changes. Here we investigated the possibility that the cell surface protein Thy-1, when interacting with a beta(3)-containing integrin on astrocytes, could trigger signaling events similar to those generated by extracellular matrix proteins. DI-TNC(1) astrocytes were stimulated with Thy-1-Fc immobilized on beads, and increased RhoA activity was confirmed using an affinity precipitation assay. The effect of various inhibitors on the cellular response was also studied. The presence of Y-27632, an inhibitor of Rho kinase (p160ROCK), a key downstream effector of RhoA, significantly reduced focal adhesion and stress fiber formation induced by Thy-1. Similar effects were obtained when astrocytes were treated with C3 transferase, an inhibitor of RhoA. Alternatively, astrocytes were transfected with an expression vector encoding fusion proteins of enhanced green fluorescent protein with either the Rho-binding domain of Rhotekin, which blocks RhoA function, or the dominant-negative N19RhoA mutant. In both cases, Thy-1-induced focal adhesion formation was inhibited. Furthermore, we observed that RhoA activity after stimulation with soluble Thy-1-Fc molecule was augmented upon further cross-linking using protein A-Sepharose beads. The same was shown by cross-linking beta(3)-containing integrin with anti-beta(3) antibodies. Together, these results indicate that Thy-1-mediated astrocyte stimulation depended on beta(3) integrin clustering and the resulting increase in RhoA activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39139-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15220352-Amides, pubmed-meshheading:15220352-Animals, pubmed-meshheading:15220352-Antigens, Thy-1, pubmed-meshheading:15220352-Astrocytes, pubmed-meshheading:15220352-Cell Adhesion, pubmed-meshheading:15220352-Cell Line, pubmed-meshheading:15220352-Extracellular Matrix, pubmed-meshheading:15220352-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:15220352-Focal Adhesions, pubmed-meshheading:15220352-Genes, Dominant, pubmed-meshheading:15220352-Integrins, pubmed-meshheading:15220352-Ligands, pubmed-meshheading:15220352-Microscopy, Fluorescence, pubmed-meshheading:15220352-Protein Binding, pubmed-meshheading:15220352-Pyridines, pubmed-meshheading:15220352-Rats, pubmed-meshheading:15220352-Recombinant Proteins, pubmed-meshheading:15220352-Time Factors, pubmed-meshheading:15220352-rhoA GTP-Binding Protein
pubmed:year
2004
pubmed:articleTitle
Aggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytes.
pubmed:affiliation
Programs of Morphology and Cell and Molecular Biology, FONDAP Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia 1027-A, Santiago, Chile.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't