Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered GEF-H1 activity a crucial determinant of disease pathogenesis?
The Rho guanine nucleotide exchange factor GEF-H1 is uniquely regulated by microtubule binding and is crucial in coupling microtubule dynamics to Rho-GTPase activation in a variety of normal biological situations. Here, we review the roles of GEF-H1 in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, and cancer. GEF-H1 might also contribute to pathophysiological signaling involved in leukemias, and in cancers associated with mutated p53 tumor suppressor gene, epithelial and endothelial cell dysfunction, infectious disease, and cardiac hypertrophy. We suggest that GEF-H1 could be a novel therapeutic target in multiple human diseases.
Birkenfeld
Jörg
J
Direvo Biotech AG, Nattermannallee 1, D-50829 Cologne, Germany.
Nalbant
Perihan
P
Yoon
Soon-Hee
SH
Bokoch
Gary M
GM
D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D004848:Epithelium / Q000473:pathology; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C577356:ARHGEF2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins