GIV/Girdin activates Gαi and inhibits Gαs via the same motif

Media type: E-Article
Title: GIV/Girdin activates Gαi and inhibits Gαs via the same motif
Contributor: Gupta, Vijay; Bhandari, Deepali; Leyme, Anthony; Aznar, Nicolas; Midde, Krishna K.; Lo, I-Chung; Ear, Jason; Niesman, Ingrid; López-Sánchez, Inmaculada; Blanco-Canosa, Juan Bautista; von Zastrow, Mark; Garcia-Marcos, Mikel; Farquhar, Marilyn G.; Ghosh, Pradipta
imprint: Proceedings of the National Academy of Sciences, 2016
Published in: Proceedings of the National Academy of Sciences, 113 (2016) 39
Language: English
DOI: 10.1073/pnas.1609502113
ISSN: 0027-8424; 1091-6490
Origination:
Footnote:
Description: <jats:title>Significance</jats:title> <jats:p>Guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV)/Girdin has previously been shown to serve as a guanine nucleotide exchange factor (GEF) for the Gα activity-inhibiting polypeptide 1 (Gαi) via a conserved motif in its C terminus. Here we show that this motif serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs. Sequential phosphorylation of two serine residues that flank this motif by two kinases, cyclin-dependent kinase 5 and PKCθ, ensures that GIV exerts its GEF and GDI activities on Gαi and Gαs, respectively, in a temporally and spatially segregated manner. Through its bifunctional role as GEF and GDI, GIV serves as a pleiotropically acting G-protein modulator that integrates, reinforces, and compartmentalizes signals downstream of both growth factors and G proteins and orchestrates migration–proliferation dichotomy.</jats:p>
Access State: Open Access

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