| http://purl.uniprot.org/citations/27621449 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27621449 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27621449 | http://www.w3.org/2000/01/rdf-schema#comment | "We previously showed that guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV), a guanine-nucleotide exchange factor (GEF), transactivates Gα activity-inhibiting polypeptide 1 (Gαi) proteins in response to growth factors, such as EGF, using a short C-terminal motif. Subsequent work demonstrated that GIV also binds Gαs and that inactive Gαs promotes maturation of endosomes and shuts down mitogenic MAPK-ERK1/2 signals from endosomes. However, the mechanism and consequences of dual coupling of GIV to two G proteins, Gαi and Gαs, remained unknown. Here we report that GIV is a bifunctional modulator of G proteins; it serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs using the same motif that allows it to serve as a GEF for Gαi. Upon EGF stimulation, GIV modulates Gαi and Gαs sequentially: first, a key phosphomodification favors the assembly of GIV-Gαi complexes and activates GIV's GEF function; then a second phosphomodification terminates GIV's GEF function, triggers the assembly of GIV-Gαs complexes, and activates GIV's GDI function. By comparing WT and GIV mutants, we demonstrate that GIV inhibits Gαs activity in cells responding to EGF. Consequently, the cAMP→PKA→cAMP response element-binding protein signaling axis is inhibited, the transit time of EGF receptor through early endosomes are accelerated, mitogenic MAPK-ERK1/2 signals are rapidly terminated, and proliferation is suppressed. These insights define a paradigm in G-protein signaling in which a pleiotropically acting modulator uses the same motif both to activate and to inhibit G proteins. Our findings also illuminate how such modulation of two opposing Gα proteins integrates downstream signals and cellular responses."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1609502113"xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1609502113"xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Bhandari D."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Bhandari D."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Ghosh P."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Ghosh P."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Gupta V."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Gupta V."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Farquhar M.G."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Farquhar M.G."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "von Zastrow M."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "von Zastrow M."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Niesman I."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Niesman I."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Ear J."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Ear J."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Aznar N."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Aznar N."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Blanco-Canosa J.B."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Blanco-Canosa J.B."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Garcia-Marcos M."xsd:string |
| http://purl.uniprot.org/citations/27621449 | http://purl.uniprot.org/core/author | "Garcia-Marcos M."xsd:string |