Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct 15;22(20):11129.
doi: 10.3390/ijms222011129.

The Role of RASGRP2 in Vascular Endothelial Cells-A Mini Review

Jun-Ichi Takino  1 , Shouhei Miyazaki  1 , Kentaro Nagamine  2 , Takamitsu Hori  1
Affiliations
Review

The Role of RASGRP2 in Vascular Endothelial Cells-A Mini Review

Jun-Ichi Takino et al. Int J Mol Sci. .

Abstract

RAS guanyl nucleotide-releasing proteins (RASGRPs) are important proteins that act as guanine nucleotide exchange factors, which activate small GTPases and function as molecular switches for intracellular signals. The RASGRP family is composed of RASGRP1-4 proteins and activates the small GTPases, RAS and RAP. Among them, RASGRP2 has different characteristics from other RASGRPs in that it targets small GTPases and its localizations are different. Many studies related to RASGRP2 have been reported in cells of the blood cell lineage. Furthermore, RASGRP2 has also been reported to be associated with Huntington's disease, tumors, and rheumatoid arthritis. In addition, we also recently reported RASGRP2 expression in vascular endothelial cells, and clarified the involvement of xenopus Rasgrp2 in the vasculogenesis process and multiple signaling pathways of RASGRP2 in human vascular endothelial cells with stable expression of RASGRP2. Therefore, this article outlines the existing knowledge of RASGRP2 and focuses on its expression and role in vascular endothelial cells, and suggests that RASGRP2 functions as a protective factor for maintaining healthy blood vessels.

Keywords: R-RAS; RAP1; RAS guanyl nucleotide-releasing protein 2 (RASGRP2); small GTPase; vascular endothelial cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Domain architecture of RASGRP2. RASGRP2 is a multidomain protein consisting of a REM region, a CDC25 domain, two EF hands, and a C1 domain. GenomeNet server (https://www.genome.jp/tools/motif/, accessed on 14 October 2021) was used to search for specific motifs in protein sequences.
Figure 2
Figure 2
Proposed model for Rasgrp2 function in hemangioblast cells. VEGF: vascular endothelial growth factor, Rasgrp2: Ras guanyl nucleotide-releasing protein 2.
Figure 3
Figure 3
Proposed model for apoptosis suppression via the RAP1 and R-RAS pathways by RASGRP2. TNF-α: tumor necrosis factor-α, TNFR: tumor necrosis factor receptor, NOX: NADPH oxidase, ROS: reactive oxygen species, RASGRP2: RAS guanyl nucleotide releasing protein 2, PI3K: phosphoinositide 3-kinase, JNK: c-jun N-terminal kinase, HK-2: hexokinase-2, VDAC: voltage-dependent anion channel, Thr: Threonine, P: phosphorylation.
Figure 4
Figure 4
Proposed model for vascular hyper-permeability suppression via the RAP1 and R-RAS pathways by RASGRP2. AGEs: advanced glycation end products, RAGE: receptor for AGEs, ZO-1: zonula occludens-1, VE-CAD: vascular endothelial-cadherin, TJs: tight junctions, AJs: adherens junctions.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Raaijmakers J.H., Bos J.L. Specificity in Ras and Rap signaling. J. Biol. Chem. 2009;284:10995–10999. doi: 10.1074/jbc.R800061200. - DOI - PMC - PubMed
    1. Stone J.C. Regulation and Function of the RasGRP Family of Ras Activators in Blood Cells. Genes Cancer. 2011;2:320–334. doi: 10.1177/1947601911408082. - DOI - PMC - PubMed
    1. Johnson J.E., Goulding R.E., Ding Z., Partovi A., Anthony K.V., Beaulieu N., Tazmini G., Cornell R.B., Kay R.J. Differential membrane binding and diacylglycerol recognition by C1 domains of RasGRPs. Biochem. J. 2007;406:223–236. doi: 10.1042/BJ20070294. - DOI - PMC - PubMed
    1. Tazmini G., Beaulieu N., Woo A., Zahedi B., Goulding R.E., Kay R.J. Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF domain. Biochim. Biophys. Acta. 2009;1793:447–461. doi: 10.1016/j.bbamcr.2008.12.019. - DOI - PubMed
    1. Czikora A., Kedei N., Kalish H., Blumberg P.M. Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3. Biochim. Biophys. Acta Biomembr. 2017;1859:2350–2360. doi: 10.1016/j.bbamem.2017.09.010. - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources