GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 03/2005; 6(2):167-80. DOI: 10.1038/nrm1587
Source: PubMed


Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to diverse extracellular stimuli, and ultimately regulate numerous cellular responses such as proliferation, differentiation and movement. With 69 distinct homologues, Dbl-related GEFs represent the largest family of direct activators of Rho GTPases in humans, and they activate Rho GTPases within particular spatio-temporal contexts. The failure to do so can have significant consequences and is reflected in the aberrant function of Dbl-family GEFs in some human diseases.

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    • "A possible mechanism for the spatio-temporal activation of Rac1 at cell-cell junctions is through localized activation of guanine-nucleotide exchange factors (GEFs); factors that activate small GTPases by promoting the exchange of bound GDP for GTP (Rossman et al., 2005). It is still unclear which of the many identified Rac-GEFs function in endothelial cells control VE-cadherin-based cell-cell junctions. "
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    • "However, the mechanisms by which mechanical force induces activation of RhoA and/or Rac1 are unknown. Rho guanine nucleotide exchange factors (Rho-GEFs) are responsible for the conversion of Rho GTPases from inactive GDP-bound forms to active GTP-bound forms, and these activated forms associate with downstream effector proteins to induce diverse cellular responses (Schmidt and Hall, 2002; Rossman et al., 2005; Cook et al., 2014). In the human genome, there are ,70 distinct members of the Dbl-related Rho-GEF gene family, and they are thought to stimulate the GDP-GTP exchange of Rho family GTPases (Cook et al., 2014). "
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