title: Phosphorylation-mediated regulation of GEFs for RhoA.
abstract: Spatio-temporal control of RhoA GTPase is critical for regulation of cell migration, attachment to extracellular matrix, and cell-cell adhesions. Activation of RhoA is mediated by guanine nucleotide exchange factors (GEFs), a diverse family of enzymes that are controlled by multiple signaling pathways regulating actin cytoskeleton and cell migration. GEFs can be regulated by different mechanisms. Growing evidence demonstrates that phosphorylation serves as one of the predominant signals controlling activity, interactions, and localization of RhoGEFs. It acts as a positive and a negative regulator, and allows for regulation of RhoGEFs by multiple signaling cascades. Although there are common trends in phosphorylation-mediated regulation of some RhoGEF homologs, the majority of GEFs utilize distinct mechanisms that are dictated by their unique structure and interaction networks. This diversity enables multiple signaling pathways to use different RhoGEFs for regulation of a single central-RhoA. Here, we review current examples of phosphorylation-mediated regulation of GEFs for RhoA and its role in cell migration, discuss mechanisms, and provide insights into potential future directions.
authors.affiliation: Department of Pharmacology; University of Illinois at Chicago; Chicago, IL USA.
authors.forename: Maulik
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Pharmacology; University of Illinois at Chicago; Chicago, IL USA.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Karginov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D051567:Proto-Oncogene Proteins c-vav; C066737:RHOA protein, human; D011494:Protein Kinases; D020742:rhoA GTP-Binding Protein
keywords: RhoA; RhoGEF; cell migration; kinase; phosphorylation