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

Oncogene volume 33, pages 4021–4035 (2014)Cite this article

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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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Acknowledgements

We thank Adrienne D Cox for careful and critical reading of our manuscript. We apologize to colleagues whose studies we did not cite due to space limitations. CJD is supported by grants from the NIH, AACR/Pancreatic Cancer Action Network and the Lustgarten Pancreatic Cancer Foundation. DRC was supported by a T32 training grant (CA71341) and an F31 predoctoral fellowship (CA159821).

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Authors and Affiliations

  1. Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA,

    D R Cook & C J Der

  2. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    K L Rossman & C J Der

  3. Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA,

    K L Rossman & C J Der

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  1. D R Cook
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  2. K L Rossman
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  3. C J Der
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Correspondence to C J Der.

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Cook, D., Rossman, K. & Der, C. Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease. Oncogene 33, 4021–4035 (2014). https://doi.org/10.1038/onc.2013.362

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  • DOI: https://doi.org/10.1038/onc.2013.362

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