Regulation of N-formyl peptide receptor signaling and trafficking by individual carboxyl-terminal serine and threonine residues

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ross M PotterEric R Prossnitz

Abstract

Adaptation, defined as the diminution of receptor signaling in the presence of continued or repeated stimulation, is critical to cellular function. G protein-coupled receptors (GPCRs) undergo multiple adaptive processes, including desensitization and internalization, through phosphorylation of cytoplasmic serine and threonine residues. However, the relative importance of individual and combined serine and threonine residues to these processes is not well understood. We examined this mechanism in the context of the N-formyl peptide receptor (FPR), a well-characterized member of the chemoattractant/chemokine family of GPCRs critical to neutrophil function. To evaluate the contributions of individual and combinatorial serine and threonine residues to internalization, desensitization, and arrestin2 binding, 30 mutant forms of the FPR, expressed in the human promyelocytic U937 cell line, were characterized. We found that residues Ser(328), Ser(332), and Ser(338) are individually critical, and indeed sufficient, for internalization, desensitization, and arrestin2 binding, but that the presence of neighboring threonine residues can inhibit these processes. Additionally, we observed no absolute correlation between arrestin binding and ...Continue Reading

References

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Citations

Oct 23, 2009·Molecular Endocrinology·Macarena PampilloAndy V Babwah
May 10, 2018·Nature Communications·Ferdinand SedlmayerMartin Fussenegger
Dec 6, 2006·The Journal of Biological Chemistry·Beatrix Pollok-KoppMartin Oppermann
Jul 23, 2013·The Journal of Biological Chemistry·Walid S MaatyAlgirdas J Jesaitis
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian A BabbinAsma Nusrat
Oct 14, 2006·Annual Review of Physiology·Catherine A C MooreJeffrey L Benovic
Feb 6, 2013·The Journal of Biological Chemistry·Lin HongAngela Wandinger-Ness
Oct 21, 2010·The Journal of Biological Chemistry·Cornelia WaltherAnnette G Beck-Sickinger
Apr 4, 2017·Biochemistry. Biokhimii︠a︡·S S Skvortsov, A G Gabdoulkhakova
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcia RiesselmanAlgirdas J Jesaitis

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