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First published online October 27, 2005
doi: 10.1242/10.1242/jcs.02671

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CZH proteins: a new family of Rho-GEFs

Nahum Meller^1,, Sylvain Merlot^2,* and Chittibabu Guda³

¹ Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
² Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA
³ Gen^*NY^*sis Center for Excellence in Cancer Genomics and Department of Epidemiology and Biostatistics, State University of New York at Albany, One University Place, Rensselaer, NY 12144, USA

View larger version (40K): [in a new window]   Fig. 1. Schematic structure of CZH proteins. The CZH1 (CDM-zizimin homology 1), CZH2 (CDM-zizimin homology 2), SH3 (Src homology 3) and PH (pleckstrin homology) domains are displayed. Areas outside the CZH1 or CZH2 domains with similarity to zizimin1 or Dock180 are hatched or crossed, respectively. Sequences obtained by computational translation are marked by asterisks. The tree represents the hypothetical evolution of the proteins based on sequence similarity. Ce, Caenorhabditis elegans; Dd, Dictyostelium discoideum; Dm, Drosophila melanogaster; Hs, Homo sapiens; Neurospora c., Neurospora crassa; S. cerevisiae, Saccharomyces cerevisiae; Trypanosoma b., Trypanosoma brucei.

View larger version (54K): [in a new window]   Fig. 2. Phylogenetic analysis of the CZH1 (a) and CZH2 (b) domains. Multiple alignments were built using the CLUSTALW program and the distances between all pairs of sequences in the multiple alignment were determined (Thompson et al., 1994). Phylogenetic trees were generated using the neighbor-joining method (Saitou and Nei, 1987) and trees were drawn using the TREEVIEW program (Page, 1996). Bar, 0.1 nucleotide substitutions per site. At, Arabidopsis thaliana; Ce, Caenorhabditis elegans; Dd, Dictyostelium discoideum; Dm, Drosophila melanogaster; Hs, Homo sapiens; Sc, Saccharomyces cerevisiae.

View larger version (19K): [in a new window]   Fig. 3. Signal transduction by Dock180. Signalling pathways where Dock180 mediates Rac activation are displayed. GPCRs, G-protein-coupled receptors; ECM, extracellular matrix.