Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells

Ricardo Hernández-García, M. Luisa Iruela-Arispe, Guadalupe Reyes-Cruz, José Vázquez-Prado*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)60-72
Number of pages13
JournalVascular Pharmacology
Volume74
DOIs
StatePublished - Nov 2015

Keywords

  • Cdc42
  • Endothelial cell cytoskeleton
  • Rac
  • Rho GTPases
  • RhoGEF
  • Tumor angiogenesis
  • VEGF

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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