TY - JOUR
T1 - Endothelial RhoGEFs
T2 - A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells
AU - Hernández-García, Ricardo
AU - Iruela-Arispe, M. Luisa
AU - Reyes-Cruz, Guadalupe
AU - Vázquez-Prado, José
N1 - Funding Information:
We acknowledge J. Silvio Gutkind, who kindly provided us several anti-RhoGEF antibodies and Estanislao Escobar-Islas, Margarita Valadez-Sánchez, David Pérez-Rangel and Jaime Estrada-Trejo for their technical assistance. This work was supported by Consejo Nacional de Ciencia y Tecnologia (CONACyT) grants 152434 (to J.V.P.) and 79429 (to G.R.C.) and by a University of California Institute for Mexico and the United States , UC-Mexus-Conacyt collaborative grant to JVP and MLIA. RHG is a graduate student supported by a CONACyT fellowship.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/11
Y1 - 2015/11
N2 - Rho guanine nucleotide exchange factors (RhoGEFs) integrate cell signaling inputs into morphological and functional responses. However, little is known about the endothelial repertoire of RhoGEFs and their regulation. Thus, we assessed the expression of 81 RhoGEFs (70 homologous to Dbl and 11 of the DOCK family) in endothelial cells. Further, in the case of DH-RhoGEFs, we also determined their responses to VEGF exposure in vitro and in the context of tumors. A phylogenetic analysis revealed the existence of four groups of DH-RhoGEFs and two of the DOCK family. Among them, we found that the most abundant endothelial RhoGEFs were: Tuba, FGD5, Farp1, ARHGEF17, TRIO, P-Rex1, ARHGEF15, ARHGEF11, ABR, Farp2, ARHGEF40, ALS, DOCK1, DOCK7 and DOCK6. Expression of RASGRF2 and PREX2 increased significantly in response to VEGF, but most other RhoGEFs were unaffected. Interestingly murine endothelial cells isolated from tumors showed that all four phylogenetic subgroups of DH-RhoGEFs were altered when compared to non-tumor endothelial cells. In summary, our results provide a detailed assessment of RhoGEFs expression profiles in the endothelium and set the basis to systematically address their regulation in vascular signaling.
AB - Rho guanine nucleotide exchange factors (RhoGEFs) integrate cell signaling inputs into morphological and functional responses. However, little is known about the endothelial repertoire of RhoGEFs and their regulation. Thus, we assessed the expression of 81 RhoGEFs (70 homologous to Dbl and 11 of the DOCK family) in endothelial cells. Further, in the case of DH-RhoGEFs, we also determined their responses to VEGF exposure in vitro and in the context of tumors. A phylogenetic analysis revealed the existence of four groups of DH-RhoGEFs and two of the DOCK family. Among them, we found that the most abundant endothelial RhoGEFs were: Tuba, FGD5, Farp1, ARHGEF17, TRIO, P-Rex1, ARHGEF15, ARHGEF11, ABR, Farp2, ARHGEF40, ALS, DOCK1, DOCK7 and DOCK6. Expression of RASGRF2 and PREX2 increased significantly in response to VEGF, but most other RhoGEFs were unaffected. Interestingly murine endothelial cells isolated from tumors showed that all four phylogenetic subgroups of DH-RhoGEFs were altered when compared to non-tumor endothelial cells. In summary, our results provide a detailed assessment of RhoGEFs expression profiles in the endothelium and set the basis to systematically address their regulation in vascular signaling.
KW - Cdc42
KW - Endothelial cell cytoskeleton
KW - Rac
KW - Rho GTPases
KW - RhoGEF
KW - Tumor angiogenesis
KW - VEGF
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U2 - 10.1016/j.vph.2015.10.003
DO - 10.1016/j.vph.2015.10.003
M3 - Article
C2 - 26471833
AN - SCOPUS:84947549132
VL - 74
SP - 60
EP - 72
JO - Vascular Pharmacology
JF - Vascular Pharmacology
SN - 1537-1891
ER -