RGD Reference Report - A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. - Rat Genome Database

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A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype.

Authors: Liu, M  Horowitz, A 
Citation: Liu M and Horowitz A, Mol Biol Cell. 2006 Apr;17(4):1880-7. Epub 2006 Feb 8.
RGD ID: 8553644
Pubmed: PMID:16467373   (View Abstract at PubMed)
PMCID: PMC1415294   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E06-01-0002   (Journal Full-text)

We identified a Rho guanine exchange factor (GEF) expressed as two splice variants, which differ only in either having or lacking a Postsynaptic density 95, Disk large, Zona occludens-1 (PDZ) motif. The PDZ adaptor protein synectin bound the longer splice variant, Syx1, which was targeted to the plasma membrane in a synectin-dependent manner. The shorter variant, Syx2, was diffusely distributed in the cytoplasm. Fluorescence resonance energy transfer (FRET) imaging revealed similar differences between the spatial patterns of active RhoA in Syx1 versus Syx2-expressing cells. Expression of Syx1 augmented endothelial cell (EC) migration and tube formation, whereas Syx2 expression did not. It appears, therefore, that synectin-dependent targeting of Syx is critical to its contribution to these EC functions. Although agonist-stimulated global RhoA activity was similar in Syx1- and Syx2-expressing cells, basal RhoA activity was surprisingly higher in the latter. Out of 23 cell types, we found a significant level of endogenous Syx2 expression only in brain tumor cells, which also exhibited high basal RhoA activity. We found that the activity level of JNK, which mediates transcriptional regulation downstream of RhoA, is elevated in a Syx2-dependent manner in these cells, possibly contributing to their tumorigenicity.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gipc1Ratprotein binding enablesIPIUniProtKB:Q6RFZ7PMID:16467373IntAct 
Plekhg5Ratprotein binding enablesIPIUniProtKB:Q9Z254PMID:16467373IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Gipc1  (GIPC PDZ domain containing family, member 1)
Plekhg5  (pleckstrin homology and RhoGEF domain containing G5)


Additional Information