Breast Cancer Research and Treatment

, Volume 84, Issue 1, pp 61–71 | Cite as

Molecular Basis for Rho GTPase Signaling Specificity

  • Antoine E. Karnoub
  • Marc Symons
  • Sharon L. Campbell
  • Channing J. Der


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.

Dbl DH domain effector GTPase oncogene Rho signaling specificity transformation 


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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Antoine E. Karnoub
    • 1
  • Marc Symons
    • 3
  • Sharon L. Campbell
    • 2
  • Channing J. Der
    • 1
  1. 1.Department of Pharmacology, Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Center for Oncology and Cell BiologyNorth Shore-LIJ Research InstituteManhassetUSA

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