title: Functional interaction between Galpha(z) and Rap1GAP suggests a novel form of cellular cross-talk.
abstract: G(z) is a member of the G(i) family of trimeric G proteins whose primary role in cell physiology is still unknown. In an ongoing effort to elucidate the cellular functions of G(z), the yeast two-hybrid system was employed to identify proteins that specifically interact with a mutationally activated form of Galpha(z). One of the molecules uncovered in this screen was Rap1GAP, a previously identified protein that specifically stimulates GTP hydrolytic activity of the monomeric G protein Rap1 and thus is believed to function as a down-regulator of Rap1 signaling. Like G(z), the precise role of Rap1 in cell physiology is poorly understood. Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Galpha(z) and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the alpha subunit, and also attenuates the ability of activated Galpha(z) to inhibit adenylyl cyclase. Structure-function analyses indicate that the first 74 amino-terminal residues of Rap1GAP, a region distinct from the catalytic core domain responsible for the GAP activity toward Rap1, is required for this interaction. Co-precipitation assays revealed that Galpha(z), Rap1GAP, and Rap1 can form a stable complex. These data suggest that Rap1GAP acts as a signal integrator to somehow coordinate and/or integrate G(z) signaling and Rap1 signaling in cells.
authors.affiliation: Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: J
authors.initials: J
authors.lastname: Meng
authors.forename: J L
authors.initials: JL
authors.lastname: Glick
authors.forename: P
authors.initials: P
authors.lastname: Polakis
authors.forename: P J
authors.initials: PJ
authors.lastname: Casey
mesh_terms: D002450:Cell Communication; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction
chemical_list: D020690:GTPase-Activating Proteins; C484658:RAP1GAP protein, human; D019204:GTP-Binding Proteins