Cell migration is a highly regulated multistep process that requires the coordinated regulation of cell adhesion, protrusion, and contraction. These processes require numerous protein-protein interactions and the activation of specific signaling pathways. The Rho family of GTPases plays a key role in virtually every aspect of the cell migration cycle. The activation of Rho GTPases is mediated by a large and diverse family of proteins; the guanine nucleotide exchange factors (RhoGEFs). GEFs work immediately upstream of Rho proteins to provide a direct link between Rho activation and cell-surface receptors for various cytokines, growth factors, adhesion molecules, and G protein-coupled receptors. The regulated targeting and activation of RhoGEFs is essential to coordinate the migratory process. In this review, we summarize the recent advances in our understanding of the role of RhoGEFs in the regulation of cell migration.
Keywords: DH, Dbl-homology; DHR, DOCK homology region; DOCK, dedicator of cytokinesis; ECM, extracellular matrix; EGF, epidermal growth factor; FA, focal adhesion; FN, fibronectin; GAP, GTPase activating protein; GDI, guanine nucleotide dissociation inhibitor; GEF, guanine nucleotide exchange factor; GPCR, G protein-coupled receptor; HGF, hepatocyte growth factor; LPA, lysophosphatidic acid; MII, myosin II; PA, phosphatidic acid; PDGF, platelet-derived growth factor; PH, pleckstrin-homology; PIP2, phosphatidylinositol 4, 5-bisphosphate; PIP3, phosphatidylinositol (3, 4, 5)-trisphosphate.; Rho GEFs; Rho GTPases; bFGF, basic fibroblast growth factor; cell migration; cell polarization; focal adhesions; guanine nucleotide exchange factors.