Inhibition of GDP/GTP Exchange on Gα Subunits by Proteins Containing G-Protein Regulatory Motifs
A novel Gα binding consensus sequence, termed G-protein regulatory (GPR) or GoLoco motif, has been identified in a growing number of proteins, which are thought to modulate G-protein signaling. Alternative roles of GPR proteins as nucleotide exchange factors or as GDP dissociation inhibitors for Gα...
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Veröffentlicht in: | Biochemistry (Easton) 2001-05, Vol.40 (17), p.5322-5328 |
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Sprache: | eng |
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Zusammenfassung: | A novel Gα binding consensus sequence, termed G-protein regulatory (GPR) or GoLoco motif, has been identified in a growing number of proteins, which are thought to modulate G-protein signaling. Alternative roles of GPR proteins as nucleotide exchange factors or as GDP dissociation inhibitors for Gα have been proposed. We investigated the modulation of the GDP/GTP exchange of Giα1, Goα, and Gsα by three proteins containing GPR motifs (GPR proteins), LGN-585-642, Pcp2, and RapIGAPII-23-131, to elucidate the mechanisms of GPR protein function. The GPR proteins displayed similar patterns of interaction with Giα1 with the following order of affinities: Giα1GDP ≫ Giα1GDPAlF4 - ≥ Giα1GTPγS. No detectable binding of the GPR proteins to Gsα was observed. LGN-585-642, Pcp2, and RapIGAPII-23-131 inhibited the rates of spontaneous GTPγS binding and blocked GDP release from Giα1 and Goα. The inhibitory effects of the GPR proteins on Giα1 were significantly more potent, indicating that Gi might be a preferred target for these modulators. Our results suggest that GPR proteins are potent GDP dissociation inhibitors for Giα-like Gα subunits in vitro, and in this capacity they may inhibit GPCR/Gi protein signaling in vivo. |
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ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi015505w |