title: GAP control: regulating the regulators of small GTPases.
abstract: The small GTPases of the Ras superfamily mediate numerous biological processes through their ability to cycle between an inactive GDP-bound and an active GTP-bound form. Among the key regulators of GTPase cycling are the GTPase-activating proteins (GAPs), which stimulate the weak intrinsic GTP-hydrolysis activity of the GTPases, thereby inactivating them. Despite the abundance of GAPs and the fact that mutations in GAP-encoding genes underlie several human diseases, these proteins have received relatively little attention. Recent studies have addressed the regulatory mechanisms that influence GAP activity. So far, findings suggest that GAP activity is regulated by several mechanisms, including protein-protein interactions, phospholipid interactions, phosphorylation, subcellular translocation and proteolytic degradation.
authors.affiliation: MGH Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Bernards
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Settleman
mesh_terms: D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D020690:GTPase-Activating Proteins; D020558:GTP Phosphohydrolases