title: Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells.
abstract: 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.
authors.affiliation: Department of Pharmacology,CINVESTAV-IPN,México D.F.,Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hernández-García
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and Molecular Biology Institute,University of California,Los Angeles, CA,USA.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
authors.affiliation: Department of Cell Biology,CINVESTAV-IPN,México D.F.,Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Reyes-Cruz
authors.affiliation: Department of Pharmacology,CINVESTAV-IPN,México D.F.,Mexico. Electronic address: jvazquez@cinvestav.mx.
authors.forename: José
authors.initials: J
authors.lastname: Vázquez-Prado
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D010802:Phylogeny; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D064067:Rho Guanine Nucleotide Exchange Factors; D042461:Vascular Endothelial Growth Factor A
keywords: Cdc42; Endothelial cell cytoskeleton; Rac; Rho GTPases; RhoGEF; Tumor angiogenesis; VEGF