Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2013, PMID: 23548900

Endomembrane H-Ras controls vascular endothelial growth factor-induced nitric-oxide synthase-mediated endothelial cell migration.

Haeussler, Dagmar J; Pimentel, David R; Hou, Xiuyun; Burgoyne, Joseph R; Cohen, Richard A; Bachschmid, Markus M

We demonstrate for the first time that endomembrane-delimited H-Ras mediates VEGF-induced activation of endothelial nitric-oxide synthase (eNOS) and migratory response of human endothelial cells. Using thiol labeling strategies and immunofluorescent cell staining, we found that only 31% of total H-Ras is S-palmitoylated, tethering the small GTPase to the plasma membrane but leaving the function of the large majority of endomembrane-localized H-Ras unexplained. Knockdown of H-Ras blocked VEGF-induced PI3K-dependent Akt (Ser-473) and eNOS (Ser-1177) phosphorylation and nitric oxide-dependent cell migration, demonstrating the essential role of H-Ras. Activation of endogenous H-Ras led to recruitment and phosphorylation of eNOS at endomembranes. The loss of migratory response in cells lacking endogenous H-Ras was fully restored by modest overexpression of an endomembrane-delimited H-Ras palmitoylation mutant. These studies define a newly recognized role for endomembrane-localized H-Ras in mediating nitric oxide-dependent proangiogenic signaling.

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Text Mining Data

endothelial nitric-oxide synthase (eNOS) → VEGF: " We demonstrate for the first time that endomembrane delimited H-Ras mediates VEGF induced activation of endothelial nitric-oxide synthase (eNOS) and migratory response of human endothelial cells "

Akt → VEGF: " Knockdown of H-Ras blocked VEGF induced PI3K dependent Akt ( Ser-473 ) and eNOS ( Ser-1177 ) phosphorylation and nitric oxide dependent cell migration, demonstrating the essential role of H-Ras "

Akt → PI3K: " Knockdown of H-Ras blocked VEGF induced PI3K dependent Akt ( Ser-473 ) and eNOS ( Ser-1177 ) phosphorylation and nitric oxide dependent cell migration, demonstrating the essential role of H-Ras "

eNOS → VEGF: " Knockdown of H-Ras blocked VEGF induced PI3K dependent Akt ( Ser-473 ) and eNOS ( Ser-1177 ) phosphorylation and nitric oxide dependent cell migration, demonstrating the essential role of H-Ras "

eNOS → PI3K: " Knockdown of H-Ras blocked VEGF induced PI3K dependent Akt ( Ser-473 ) and eNOS ( Ser-1177 ) phosphorylation and nitric oxide dependent cell migration, demonstrating the essential role of H-Ras "

eNOS → H-Ras: " Activation of endogenous H-Ras led to recruitment and phosphorylation of eNOS at endomembranes "

Manually curated Databases

No curated data.