Linked Life Data

11287419

Source:http://linkedlifedata.com/resource/pubmed/id/11287419

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-6-11
pubmed:abstractText
CYR61, an angiogenic factor and a member of the CCN protein family, is an extracellular matrix-associated, heparin-binding protein that mediates cell adhesion, promotes cell migration, and enhances growth factor-stimulated cell proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and is expressed in dermal fibroblasts during cutaneous wound healing. It has been demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is mediated through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans, resulting in adhesive signaling and up-regulation of matrix metalloproteinases 1 and 3. CYR61 is composed of four discrete structural domains that bear sequence similarities to the insulin-like growth factor-binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a carboxyl-terminal (CT) domain that resembles cysteine knots found in some growth factors. In this study, we show that a CYR61 mutant (CYR61DeltaCT) that has the CT domain deleted is unable to support adhesion of primary human skin fibroblasts but is still able to stimulate chemotaxis and enhance basic fibroblast growth factor-induced mitogenesis similar to wild type. In addition, fibroblast migration to CYR61 is mediated through integrin alpha(v)beta(5) but not integrins alpha(6)beta(1) or alpha(v)beta(3). Furthermore, we show that CYR61 binds directly to purified integrin alpha(v)beta(5) in vitro. By contrast, CYR61 enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated through integrin alpha(v)beta(3), a known receptor for CYR61 that mediates CYR61-dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61 promotes primary human fibroblast adhesion, migration, and mitogenesis through integrins alpha(6)beta(1), alpha(v)beta(5), and alpha(v)beta(3), respectively. Together, these findings establish CYR61 as a novel ligand for integrin alpha(v)beta(5) and show that CYR61 interacts with distinct integrins to mediate disparate activities in a cell type-specific manner.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21943-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11287419-Animals, pubmed-meshheading:11287419-Cell Adhesion, pubmed-meshheading:11287419-Cell Division, pubmed-meshheading:11287419-Cell Line, pubmed-meshheading:11287419-Cell Movement, pubmed-meshheading:11287419-Cysteine-Rich Protein 61, pubmed-meshheading:11287419-DNA, pubmed-meshheading:11287419-Fibroblasts, pubmed-meshheading:11287419-Growth Substances, pubmed-meshheading:11287419-Humans, pubmed-meshheading:11287419-Immediate-Early Proteins, pubmed-meshheading:11287419-Insects, pubmed-meshheading:11287419-Integrins, pubmed-meshheading:11287419-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:11287419-Kinetics, pubmed-meshheading:11287419-Mutagenesis, pubmed-meshheading:11287419-Receptors, Vitronectin, pubmed-meshheading:11287419-Recombinant Proteins, pubmed-meshheading:11287419-Sequence Deletion, pubmed-meshheading:11287419-Skin, pubmed-meshheading:11287419-Skin Physiological Phenomena, pubmed-meshheading:11287419-Thymidine, pubmed-meshheading:11287419-Transfection
pubmed:year
2001
pubmed:articleTitle
CYR61 stimulates human skin fibroblast migration through Integrin alpha vbeta 5 and enhances mitogenesis through integrin alpha vbeta 3, independent of its carboxyl-terminal domain.
pubmed:affiliation
Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.