Molecular basis for Rho GTPase signaling specificity.
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.
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Antoine E
AE
Karnoub
Marc
M
Symons
Sharon L
SL
Campbell
Channing J
CJ
Der
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D020690:GTPase-Activating Proteins / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D006801:Humans; D009154:Mutation; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D020690:GTPase-Activating Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D020662:Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins