Ras guanyl nucleotide releasing protein 2 affects cell viability and cell–matrix adhesion in ECV304 endothelial cells

Takino, Junichi; Nagamine, Kentaro; Hori, Takamitsu

doi:10.4161/cam.24082

Cited by 8 publications

(10 citation statements)

References 31 publications

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“…In human ECs, CalDAG-GEF1 has been implicated in both Ras and Rap1 pathways: its overexpression leads to increased expression of Ras, but increased activity only of Rap1, through which it promotes EC adhesion and migration [21]. …”

Section: Genetic Modelsmentioning

confidence: 99%

Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction

Chrzanowska‐Wodnicka

2013

Experimental Cell Research

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Rap1 signaling is important for both major processes of vessel formation: vasculogenesis, or de novo vessel formation, and angiogenesis, sprouting of new vessels from pre-existing ones. We provide an overview of genetic studies in mice and zebrafish and discuss some of the proposed underlying mechanisms derived from cellular models, with particular emphasis on Rap1's role in angiogenesis, maintenance of endothelial barrier and connection with cerebral cavernous malformation (CCM), a neurological deficit that leads to seizures and lethal stroke. Lastly, we provide a brief summary of studies in cardiac and smooth muscle cells, where the Epac-Rap1 signaling axis is emerging as an important regulator of contractility.

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Section: Genetic Modelsmentioning

confidence: 99%

Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction

Chrzanowska‐Wodnicka

2013

Experimental Cell Research

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“…We have identified Xenopus RAS guanyl releasing protein 2 (RASGRP2) as a blood vessel related gene from Xenopus embryo [7–9]. Furthermore, we reported that Xenopus RASGRP2 has highly homology to human RASGRP2 [8].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, we reported that Xenopus RASGRP2 has highly homology to human RASGRP2 [8]. RASGRP2 is well known as guanine nucleotide exchange factor (GEF) [9]. GEF stimulates guanosine triphosphate (GTP) loading of small G proteins and are competed by GTPase activating proteins which catalyzes GTP hydrolysis [10].…”

Section: Introductionmentioning

confidence: 99%

RASGRP2 Suppresses Apoptosis via Inhibition of ROS Production in Vascular Endothelial Cells

Sato

Takino

Nagamine

et al. 2019

The Scientific World Journal

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We have identified ras guanyl releasing protein 2 (rasgrp2) as a blood vessel related gene from Xenopus embryo. In addition, we reported that RASGRP2 is also expressed in human umbilical vein endothelial cells (HUVEC). It is known that RASGRP2 activates Ras-related protein 1 (Rap1). However, the function of RASGRP2 in human vascular endothelium remains unknown. Therefore, we performed functional analysis of RASGRP2 using immortalized HUVEC (TERT HUVEC). We established a stable RASGRP2 overexpressing cell line (TERT HUVEC R) and mock cell line (mock). Furthermore, we compared the activity of Rap1 and the generation of intracellular reactive oxygen species (ROS), which is related to cell death, in both cell lines. Significant increase in Rap1 activity was observed in the TERT HUVEC R compared to the mock. Furthermore, apoptosis by tumor necrosis factor-α (TNF-α) stimulation was significantly more reduced in the TERT HUVEC R than in the mock. In the mock, apoptosis induced by TNF-α stimulation was decreased by pretreatment with diphenyleneiodonium (DPI), which is an inhibitor of NADPH oxidase (NOX). However, in the TERT HUVEC R, apoptosis induced by TNF-α stimulation was not reduced after pretreatment of DPI. Furthermore, there was no reduction in ROS production in the TERT HUVEC R after DPI pretreatment. In addition, the difference in the degree of apoptosis induced by TNF-α stimulation in both cell lines was consistent with the difference in ROS production in the cell lines. From these results, it was suggested that RASGRP2 activates Rap1 and the activated Rap1 suppresses apoptosis via NOX inhibition.

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“…Proteins related to cellematrix interaction, such as integrin [27], focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/ threonine kinase (AKT) pathway [28], ras guanyl nucleotide releasing proteins (RasGRPs) [29] and transforming growth factor type I (TGF) [30], had been reported to function differently in regulating cell proliferation and the responding to drug treatments in cells cultured on different matrix. Whether one or more of these Fig.…”

Section: Discussionmentioning

confidence: 99%