| First Author | Iwashita S | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 6 | Pages | 3413-7 |
| PubMed ID | 17179160 | Mgi Jnum | J:120930 |
| Mgi Id | MGI:3708395 | Doi | 10.1074/jbc.C600293200 |
| Citation | Iwashita S, et al. (2007) Versatile roles of R-Ras GAP in neurite formation of PC12 cells and embryonic vascular development. J Biol Chem 282(6):3413-7 |
| abstractText | Ras GTPase-activating proteins (GAP) are negative regulators of Ras that convert active Ras-GTP to inactive Ras-GDP. R-Ras GAP is a membrane-associated molecule with stronger GAP activity for R-Ras, an activator of integrin, than H-Ras. We found that R-Ras GAP is down-regulated during neurite formation in rat pheochromocytoma PC12 cells by nerve growth factor (NGF), which is blocked by the transient expression of R-Ras gap or dominant negative R-ras cDNA. By establishing a PC12 subclone that stably expresses exogenous R-Ras GAP, it was found that NGF reduced endogenous R-Ras GAP but not exogenous R-Ras GAP, suggesting that down-regulation of R-Ras GAP occurs at the transcription level. To clarify the physiological role of R-Ras GAP, we generated mice that express mutant Ras GAP with knocked down activity. While heterozygotes are normal, homozygous mice die at E12.5-13.5 of massive subcutaneous and intraparenchymal bleeding, probably due to underdeveloped adherens junctions between capillary endothelial cells. These results show essential roles of R-Ras GAP in development and differentiation: its expression is needed for embryonic development of blood vessel barriers, whereas its down-regulation facilitates NGF-induced neurite formation of PC12 cells via maintaining activated R-Ras. |
