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Rho guanine nucleotide exchange factor

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Function

Rho guanine nucleotide exchange factor (GEF) stimulate the exchange of the inactive GDP-bound GTPase to its active GTP-bound form. Binding of GEF to GDP-GTPase catalyzes the dissociation of GDP from the protein[1]. GEF domains include the catalytic DH/PH (Dbl Homology/Pleckstrin Homology) domain; the CH (Calponin Homology) domain is believed to be involved in calcium regulation; the SH3 domain interacts with proline-rich sequences.

  • Rho guanine nucleotide exchange factor 1 binds to G proteins and stimulate Rho-dependent signals.
  • Rho guanine nucleotide exchange factor 6 acts on RAC1.

Disease

Increased GEF activity is involved in cancer cell proliferation by affecting Rho GTPases [2].

3D Structures of Rho guanine nucleotide exchange factor

Rho guanine nucleotide exchange factor 3D structures


Human Rho guanine nucleotide exchange factor 11 DH/PH domain (grey) complex with transforming protein RhoA (cyan), GSP and Mg+2 ion (green) (PDB code 3kz1)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Cherfils J, Zeghouf M. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev. 2013 Jan;93(1):269-309. doi: 10.1152/physrev.00003.2012. PMID:23303910 doi:http://dx.doi.org/10.1152/physrev.00003.2012
  2. ↑ Cook DR, Rossman KL, Der CJ. Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease. Oncogene. 2014 Jul 31;33(31):4021-35. doi: 10.1038/onc.2013.362. Epub 2013 Sep, 16. PMID:24037532 doi:http://dx.doi.org/10.1038/onc.2013.362

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Michal Harel, Joel L. Sussman
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