|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
Pt 17
|
|
pubmed:dateCreated |
2003-8-1
|
|
pubmed:abstractText |
Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for alpha 6 beta 4 integrin. We investigated the role of alpha 6 beta 4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective beta 4 integrin in beta 4 integrin null keratinocytes. We found that expression of beta 4 integrin in either a ligand bound or ligand unbound state was necessary and sufficient for EGF-induced cell migration. In a ligand bound state, beta 4 integrin supported EGF-induced cell migration though sustained activation of Rac1. In the absence of alpha 6 beta 4 integrin ligation, Rac1 activation became tempered and EGF chemotaxis proceeded through an alternate mechanism that depended upon alpha 3 beta 1 integrin and was characterized by cell scattering. alpha 3 beta 1 integrin also relocalated from cell-cell contacts to sites of basal clustering where it displayed increased conformational activation. The aberrant distribution and activation of alpha 3 beta 1 integrin in attachment-defective beta 4 cells could be reversed by the activation of Rac1. Conversely, in WT beta 4 cells the normal cell-cell localization of alpha 3 beta 1 integrin became aberrant after the inhibition of Rac1. These studies indicate that the extracellular domain of beta 4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors so that coordinated keratinocyte migration can be achieved.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0021-9533
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
116
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
3543-56
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:12865436-Cell Adhesion Molecules,
pubmed-meshheading:12865436-Cell Movement,
pubmed-meshheading:12865436-Chemotaxis,
pubmed-meshheading:12865436-Cloning, Molecular,
pubmed-meshheading:12865436-Epidermal Growth Factor,
pubmed-meshheading:12865436-Epidermolysis Bullosa,
pubmed-meshheading:12865436-Humans,
pubmed-meshheading:12865436-Integrin alpha3beta1,
pubmed-meshheading:12865436-Integrin alpha6beta4,
pubmed-meshheading:12865436-Intercellular Junctions,
pubmed-meshheading:12865436-Keratinocytes,
pubmed-meshheading:12865436-Microscopy, Fluorescence,
pubmed-meshheading:12865436-Mutation,
pubmed-meshheading:12865436-Protein Binding,
pubmed-meshheading:12865436-Protein Conformation,
pubmed-meshheading:12865436-Protein Structure, Tertiary,
pubmed-meshheading:12865436-Pseudopodia,
pubmed-meshheading:12865436-Wound Healing,
pubmed-meshheading:12865436-cdc42 GTP-Binding Protein,
pubmed-meshheading:12865436-rac1 GTP-Binding Protein,
pubmed-meshheading:12865436-rhoA GTP-Binding Protein
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Alpha 6 beta 4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of alpha 3 beta 1 integrin.
|
|
pubmed:affiliation |
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
