Regulation of endothelial cell adherens junctions by a Ras-dependent signal transduction pathway.
Adherens junctions, consisting of transmembrane cadherin molecules and their associated cytoplasmic alpha-, beta-, and gamma-catenin proteins, are thought to be critical for the development of stable cell adhesion and subsequent 3-dimensional tissue organization. In human endothelial cells there is a marked induction of gamma-catenin levels when cells reach confluence. We demonstrate that expression of a dominant negative ras gene product (N17ras) via adenoviral mediated gene transfer inhibits the confluent-dependent rise in gamma-catenin mRNA and protein levels. Consistent with its effects on overall gamma-catenin levels, expression of N17ras also reduces the amount of gamma-catenin associated with the adherens junction. Finally, although expression of N17ras under normal culture conditions produces no clear morphological phenotype, endothelial cells expressing a dominant negative ras gene product fail to form 3-dimensional, vascular-like structures when plated on reconstituted extracellular matrix.
Hegland
D D
DD
Cardiology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, 20892, USA.
Sullivan
D M
DM
Rovira
I I
II
Li
A
A
Kovesdi
I
I
Bruder
J T
JT
Finkel
T
T
D000256:Adenoviridae / Q000235:genetics; D002448:Cell Adhesion; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D051180:Desmoplakins; D004730:Endothelium, Vascular / Q000166:cytology*; D019084:Fluorescent Antibody Technique, Indirect; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051185:gamma Catenin; D018631:ras Proteins / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D012333:RNA, Messenger; D051185:gamma Catenin; D018631:ras Proteins