GEF what? Dock180 and related proteins help Rac to polarize cells in new ways

Trends Cell Biol. 2007 Aug;17(8):383-93. doi: 10.1016/j.tcb.2007.05.001. Epub 2007 Aug 31.


Rho GTPase activation, which is mediated by guanine nucleotide exchange factors (GEFs), is tightly regulated in time and space. Although Rho GTPases have a significant role in many biological events, they are best known for their ability to restructure the actin cytoskeleton profoundly through the activation of specific downstream effectors. Two distinct families of GEFs for Rho GTPases have been reported so far, based on the features of their catalytic domains: firstly, the classical GEFs, which contain a Dbl homology-pleckstrin homology domain module with GEF activity, and secondly, the Dock180-related GEFs, which contain a Dock homology region-2 domain that catalyzes guanine nucleotide exchange on Rho GTPases. Recent exciting data suggest key roles for the DHR-2 domain-containing GEFs in a wide variety of fundamentally important biological functions, including cell migration, phagocytosis of apoptotic cells, myoblast fusion and neuronal polarization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Fusion
  • Cell Membrane / metabolism
  • Cell Polarity*
  • Cytoskeletal Proteins
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Humans
  • Models, Biological
  • Multiprotein Complexes
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Structure, Tertiary
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Ced-12 protein, Drosophila
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Multiprotein Complexes
  • Phosphatidylinositol Phosphates
  • mbc protein, Drosophila
  • phosphatidylinositol 3,4,5-triphosphate
  • rac GTP-Binding Proteins