ArticleThe Journal of biological chemistry2011
Phosphorylation-dependent C-terminal binding of 14-3-3 proteins promotes cell surface expression of HIV co-receptor GPR15.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Mechanisms of XCR1 Membrane Trafficking and Constitutive Endocytosis.Basic & clinical pharmacology & toxicology · 2026Article
- GPR15-guided CD8Nature · 2026Article
- Modulating GPCR and 14-3-3 protein interactions: Prospects for CNS drug discovery.Drug discovery today · 2023Review
- Emerging roles of a chemoattractant receptor GPR15 and ligands in pathophysiology.Frontiers in immunology · 2023Review
- The Role of GPR15 Function in Blood and Vasculature.International journal of molecular sciences · 2021Review
- Tyrosine sulfation and O-glycosylation of chemoattractant receptor GPR15 differentially regulate interaction with GPR15L.Journal of cell science · 2021Article
- Conserved C-terminal motifs in odorant receptors instruct their cell surface expression and cAMP signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- G Protein-Coupled Receptors in the Sweet Spot: Glycosylation and other Post-translational Modifications.ACS pharmacology & translational science · 2020Review
- Analysis of Interactions Stabilized by Fusicoccin A Reveals an Expanded Suite of Potential 14-3-3 Binding Partners.ACS chemical biology · 2020Article
- 14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking.Scientific reports · 2019Article
- Rare susceptibility variants for bipolar disorder suggest a role for G protein-coupled receptors.Molecular psychiatry · 2018Article
- Review
- Differential phosphorylation signals control endocytosis of GPR15.Molecular biology of the cell · 2017Article
- Activation of GPR15 and its involvement in the biological effects of smoking.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D₂ Dopamine Receptor (D2L-R) Acts as an Intracellular Retention Signal.International journal of molecular sciences · 2016Article
- ERK2 phosphorylates Krüppel-like factor 8 protein at serine 48 to maintain its stability.American journal of cancer research · 2016Article
- Phosphoregulatory protein 14-3-3 facilitates SAC1 transport from the endoplasmic reticulum.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Minireview: Role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Molecular determinants of the human α2C-adrenergic receptor temperature-sensitive intracellular traffic.Molecular pharmacology · 2015Article
- 14-3-3θ facilitates plasma membrane delivery and function of mechanosensitive connexin 43 hemichannels.Journal of cell science · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane trafficking is dictated by dynamic molecular interactions involving discrete determinants in the cargo proteins and the intracellular transport machineries. We have previously reported that cell surface expression of GPR15, a G protein-coupled receptor (GPCR) that serves as a co-receptor for HIV, is correlated with the mode III binding of 14-3-3 proteins to the receptor C terminus. Here we provide a mechanistic basis for the role of 14-3-3 in promoting the cell surface expression of GPR15. The Ala mutation of penultimate phospho-Ser (S359A) that abolishes 14-3-3 binding resulted in substantially reduced O-glycosylation and the cell surface expression of GPR15. The surface membrane protein CD8 fused with the C-terminal tail of GPR15(S359A) mutant was re-localized in the endoplasmic reticulum (ER). In the context of S359A mutation, the additional mutations in the upstream stretch of basic residues (RXR motif) restored O-glycosylation and the cell surface expression. The RXR motif was responsible for the interaction with coatomer protein I (COPI), which was inversely correlated with the 14-3-3 binding and cell surface expression. These results suggest that 14-3-3 binding promotes cell surface expression of GPR15 by releasing the receptor from ER retrieval/retention pathway that is mediated by the interaction of RXR motif and COPI. Moreover, 14-3-3 binding substantially increased the stability of GPR15 protein. Thus 14-3-3 proteins play multiple roles in biogenesis and trafficking of an HIV co-receptor GPR15 to control its cell surface density in response to the phosphorylation signal.
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