Erk1 and Erk2 Regulate Endothelial Cell Proliferation and Migration during Mouse Embryonic Angiogenesis

Abstract

Angiogenesis is a complex process orchestrated by both growth factors and cell adhesion and is initiated by focal degradation of the vascular basement membrane with subsequent migration and proliferation of endothelial cells. The Ras/Raf/MEK/ERK pathway is required for EC function during angiogenesis. Although in vitro studies implicate ERK1 and ERK2 in endothelial cell survival, their precise role in angiogenesis in vivo remains poorly defined. Cre/loxP technology was used to inactivate Erk1 and Erk2 in endothelial cells during murine development, resulting in embryonic lethality due to severely reduced angiogenesis. Deletion of Erk1 and Erk2 in primary endothelial cells resulted in decreased cell proliferation and migration, but not in increased apoptosis. Expression of key cell cycle regulators was diminished in the double knockout cells, and decreased DNA synthesis could be observed in endothelial cells during embryogenesis. Interestingly, both Paxillin and Focal Adhesion Kinase were expressed at lower levels in endothelial cells lacking Erk1 and Erk2 both in vivo and in vitro, leading to defects in the organization of the cytoskeleton and in cell motility. The regulation of Paxillin and Focal Adhesion Kinase expression occurred post-transcriptionally. These results demonstrate that ERK1 and ERK2 coordinate endothelial cell proliferation and migration during angiogenesis.

Common Angiogenic Signaling Pathways Induced by Monomeric C - reactive protein and FGF-2 through MAPK and PI3K

“…However, the blockade of γ-secretase activity did not affect FGF-2-induced cell migration. The importance of MAPK and PI3K signaling pathways in FGF-2-induced endothelial cell migration was also confirmed by previous studies [55,56]. Here, PI3K blockade results in a full inhibition of BAEC migration induced by mCRP, while mCRPinduced distance of cell migration was remained unaffected after either MAPK or γ-secretase blockade.…”

Transcriptional Repression of Mad-Max Complex by Human Umbilical Cord Blood Stem Cells Downregulates Extracellular Signal-Regulated Kinase in Glioblastoma

“…Previous studies have demonstrated that integrin signaling through FAK plays an important role in the regulation of cell cycle progression correlating with changes in the expression of cyclin D1 [16]. In another study, ERK acts downstream of Src-FAK signaling [17,18] and upstream to regulate FAK and Paxillin expression [19]. In the present study we found that c-Myc associates and interacts with FAK.…”

Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

“…9). Although it has been reported that Arf6 is required for activation of MAPK ERK1/2 and the small G protein Rac1 in HGFstimulated epithelial cells 20 , which are implicated in endothelial cell migration 31,32 , no difference in activation of MAPKs, such as ERK1/2, p38 and JNK, Akt and Rac1 was observed for Arf6 À / À iECs in comparison with control iECs (Supplementary Fig. 10), eliminating these signalling pathways and outputs from further consideration.…”