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Molecular Basis for Rho GTPase Signaling Specificity

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Abstract

There is now considerable evidence for the involvement of aberrant Rho GTPase activation in breast cancer development. Like Ras, Rho GTPases function as signaling nodes regulated by diverse extracellular stimuli. Rho GTPase activation is facilitated by multiple regulatory proteins, in particular guanine nucleotide exchange factors (GEFs) such as Dbl family proteins. Activated Rho GTPases in turn interact with and regulate a spectrum of functionally diverse downstream effectors, initiating a network of cytoplasmic and nuclear signaling cascades. Thus, Rho GTPases represent points of signaling convergence as well as relay switches that disseminate signaling divergence. In this review, we highlight issues relating to the structural basis by which Dbl family GEFs facilitate signaling convergence and Rho GTPase activation, and how Rho GTPases promote signal dissemination through downstream effectors.

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Authors and Affiliations

  1. Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Antoine E. Karnoub & Channing J. Der

  2. Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Sharon L. Campbell

  3. Center for Oncology and Cell Biology, North Shore-LIJ Research Institute, Manhasset, NY, USA

    Marc Symons

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  1. Antoine E. Karnoub
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  4. Channing J. Der
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Karnoub, A.E., Symons, M., Campbell, S.L. et al. Molecular Basis for Rho GTPase Signaling Specificity. Breast Cancer Res Treat 84, 61–71 (2004). https://doi.org/10.1023/B:BREA.0000018427.84929.5c

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