H-Ras is a negative regulator of alpha3beta1 integrin expression in ECV304 endothelial cells.
We have examined the role of Ras in integrin expression in ECV304 endothelial cells. Among the integrins examined in stable ECV304 transfectants expressing dominant active H-Ras (DAR-ECV), expression of alpha3beta1 integrin showed a prominent reduction in all the DAR-ECV clones when compared to the parental ECV304 cells. This implies that H-Ras negatively regulates the expression of alpha3beta1 integrin in ECV304 cells. When treated with inhibitors of the Ras downstream pathway (LY294002, PD98059, SB203580), the expression of alpha3beta1 integrin was up-regulated most significantly by LY294002, suggesting that among the downstream pathways of Ras, phosphatidylinositol 3-kinase is a major determinant. With the application of blocking antibody to alpha3beta1 integrin (2 - 2 x 10(4) nM), migration of ECV304 cells was enhanced to maximal (18%) at 20 nM. These results suggest that migration of endothelial cells could be modulated by H-Ras via alteration of the expression levels of alpha3beta1 integrin.
Shin
E Y
EY
Department of Biochemistry, College of Medicine, Cheongju, Korea.
Lee
J Y
JY
Park
M K
MK
Jeong
G B
GB
Kim
E G
EG
Kim
S Y
SY
D000906:Antibodies / Q000494:pharmacology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039201:Integrin alpha3beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D039201:Integrin alpha3beta1; D016023:Integrins; D009025:Morpholines; D015689:Oncogene Protein p21(ras); D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one