title: Cyclic AMP-dependent activation of Rap1b.
abstract: Rap1 proteins belong to the Ras superfamily of small molecular weight GTP-binding proteins. Although Rap1 and Ras share approximately 50% overall amino acid sequence identity, the effector domains of the two proteins are identical, suggesting either similar or antagonistic signaling roles. Several pathways leading to Ras activation have been defined, including those initiated by agonist binding to tyrosine kinase or Gi-coupled receptors. Nothing is known about such events for Rap1 proteins. The cAMP-mediated inhibition of Ras-dependent MAP kinase activation is well documented and resembles that caused by expression of GTPase-deficient Rap1. We have developed a system whereby signals leading to Rap1b activation, i.e. an increase in Rap1b-bound GTP/GDP ratio, can be measured. We report here that treatment of cells with agents that elevate intracellular cAMP levels result in Rap1b activation. These results demonstrate for the first time agonist-dependent activation of Rap1 proteins.
authors.affiliation: Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710-0001, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Altschuler
authors.forename: S N
authors.initials: SN
authors.lastname: Peterson
authors.forename: M C
authors.initials: MC
authors.lastname: Ostrowski
authors.forename: E G
authors.initials: EG
authors.lastname: Lapetina
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017368:Protein Prenylation; D011994:Recombinant Proteins; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D020668:rap GTP-Binding Proteins
chemical_list: D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins