Catching a GEF by its tail.
The activation of Rho GTPases is mediated by guanine-nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP. Rho-GEFs are a very diverse family, with >70 members in humans. Bioinformatics analysis of the human Rho-GEFs shows that approximately 40% contain a putative PDZ-binding motif at the C-terminus. PDZ domains are protein-protein interaction domains that act as scaffolds to concentrate signaling molecules at specialized regions in the cell. We propose that the interaction between Rho-GEFs and PDZ-domain proteins is a general mechanism that controls Rho-GEF targeting and activation, helping to restrict and concentrate the exchange activity to appropriate subcellular destinations. Here, we summarize recent data that highlight the importance of these interactions in Rho-GEF regulation.
García-Mata
Rafael
R
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 12-026 Lineberger, CB#7295, Chapel Hill, NC 27599, USA. rafaelgm@med.unc.edu <rafaelgm@med.unc.edu>
Burridge
Keith
K
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology
D020033:Protein Isoforms; D011506:Proteins; D020741:rho GTP-Binding Proteins