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Cited by 127Receptor Mechanisms and SignalingCellular transport and secretionIon Transport and Channel Regulation

A serine cluster prevents recycling of the V2 vasopressin receptor

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Innamorati, Giulio, Sadeghi, Hamid M., Tran, Nathaniel T., Birnbaumer, Mariel·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.5.2222PMC PMC19299
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Abstract

Receptor recycling plays a critical role in the regulation of cellular responsiveness to environmental stimuli. Agonist-promoted phosphorylation of G protein-coupled receptors has been related to their desensitization, internalization, and sequestration. Dephosphorylation of internalized G protein-coupled receptors by cytoplasmic phosphatases has been shown to be pH-dependent, and it has been postulated to be necessary for receptors to recycle to the cell surface. The internalized V2 vasopressin receptor (V2R) expressed in HEK 293 cells is an exception to this hypothesis because it does not recycle to the plasma membrane for hours after removal of the ligand. Because this receptor is phosphorylated only by G protein-coupled receptor kinases (GRKs), the relationship between recycling and GRK-mediated phosphorylation was examined. A nonphosphorylated V2R, truncated upstream of the GRK phosphorylation sites, rapidly returned to the cell surface after removal of vasopressin. Less-drastic truncations of V2R revealed the presence of multiple phosphorylation sites and suggested a key role for a serine cluster present at the C terminus. Replacement of any one of Ser-362, Ser-363, or Ser-364 with Ala allowed quantitative recycling of full-length V2R without affecting the extent of internalization. Examination of the stability of phosphate groups incorporated into the recycling S363A mutant V2Rs revealed that the recycling receptor was dephosphorylated after hormone withdrawal, whereas the wild-type V2R was not, providing molecular evidence for the hypothesis that GRK sites must be dephosphorylated prior to receptor recycling. These experiments uncovered a role for GRK phosphorylation in intracellular sorting and revealed a GRK-dependent anchoring domain that blocks V2R recycling.

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  • A new phosphorylation site in OTR of Callithrix at R149S and shortening of a Ser cluster in OTR of Saguinus important for beta-arrestin mediated desensitization and receptor recycling were identified.

    “Additionally, (Vargas-Pinilla et al., 2015) identified a new phosphorylation site in the OTR of Callithrix at R149S, and the shortening of a Ser cluster in the OTR of Saguinus that is important for β-arrestin mediated desensitization and receptor recycling (Innamorati et al., 1998; Oakley et al., 2001; Vargas-Pinilla et al., 2015).”

    From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Innamorati et al., 1998

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Research works printed but not linked: 6

  1. [2]Innamorati, G., Sadeghi, H. & Birnbaumer, M. (1998) J. Biol. Chem. 273, in press. [DOI] [PubMed]
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Authors
Innamorati, G., Sadeghi, H. M., Tran, N. T., & Birnbaumer, M.
Affiliations
  • University of California, Los Angeles (US)
  • Department of Anesthesiology and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095
Corresponding author
Birnbaumer, Mariel
ORCID
Innamorati, Giulio
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1998-03-03
Volume
95
Issue
5
Pages
2222-2226
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.95.5.2222
PMC
PMC19299
OpenAlex
W2090664128
Cited by
127
References
17
Citations by year
2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
4.07
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK-41244)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
V2 receptor, receptor recycling, G protein-coupled receptor kinases, receptor internalization, dephosphorylation, receptor desensitization, intracellular sorting
MeSH terms
Amino Acid Sequence, Arginine Vasopressin, Cell Line, Cell Membrane, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Conformation, Recombinant Fusion Proteins, Serine, Transfection, Mutagenesis, Site-Directed, Receptors, Vasopressin, GTP-Binding Proteins, Amino Acid Substitution, Receptor Protein-Tyrosine Kinases

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