Cited by 378Protein Kinase Regulation and GTPase SignalingCellular transport and secretionHippo pathway signaling and YAP/TAZ

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

Open access
Cook, D R, Rossman, K L, Der, C J·2014·Oncogene

Abstract

The aberrant activity of Ras homologous (Rho) family small GTPases (20 human members) has been implicated in cancer and other human diseases. However, in contrast to the direct mutational activation of Ras found in cancer and developmental disorders, Rho GTPases are activated most commonly in disease by indirect mechanisms. One prevalent mechanism involves aberrant Rho activation via the deregulated expression and/or activity of Rho family guanine nucleotide exchange factors (RhoGEFs). RhoGEFs promote formation of the active GTP-bound state of Rho GTPases. The largest family of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 human members. The multitude of RhoGEFs that activate a single Rho GTPase reflects the very specific role of each RhoGEF in controlling distinct signaling mechanisms involved in Rho activation. In this review, we summarize the role of Dbl RhoGEFs in development and disease, with a focus on Ect2 (epithelial cell transforming squence 2), Tiam1 (T-cell lymphoma invasion and metastasis 1), Vav and P-Rex1/2 (PtdIns(3,4,5)P3 (phosphatidylinositol (3,4,5)-triphosphate)-dependent Rac exchanger).

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Crossref · 10.1038/onc.2013.362

Cites

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  • DH GEFs constitute the larger of the two classes, with over 70 members.

    “DH GEFs constitute the larger of the two classes, with over 70 members (30, 31).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [30]

    In “The discovery of RhoGEFs: diverse in numbers and structure” (page not supplied), the paper reports 70 human Dbl-family RhoGEFs and 11 human DOCK-family RhoGEFs. This supports that the DH/Dbl class is larger, but not the claim that it has over 70 members. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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1 retracted

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3 of the 230 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [80]Sahai E Marshall CJ RHO–GTPase and cancer Nat Rev Cancer 2002 2 133 142 12635176

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Authors
Cook, D. R., Rossman, K. L., & Der, C. J.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Der, C J
Venue
Oncogene
Published
2013-09-16
Volume
33
Issue
31
Pages
4021-4035
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2024222958
Cited by
378
References
230
Citations by year
2026: 14 · 2025: 15 · 2024: 17 · 2023: 26 · 2022: 35 · 2021: 45 · 2020: 43 · 2019: 33 · 2018: 37 · 2017: 29 · 2016: 34 · 2015: 24 · 2014: 23 · 2013: 3
FWCI
2.64
Type
journal article
Language
en
Open access
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • Pancreatic Cancer Action Network
  • National Institutes of Health (5r01ca042978-30)
  • National Cancer Institute (CA159821, CA 71341, R01-CA042978, F31CA159821, T32CA071341)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
RhoGEF, Rho GTPases, ECT2, Tiam1, Vav, Rho activation, cancer, developmental disorders, phosphatidylinositol 3,4,5-trisphosphate, small GTPase signaling
MeSH terms
Congenital Abnormalities, Animals, Cell Division, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, rho GTP-Binding Proteins, Genetic Diseases, Inborn, Proto-Oncogene Proteins c-vav, Rho Guanine Nucleotide Exchange Factors

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