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Phosphorylation of intracellular serine and threonine residues is the most important post translational modification of G protein-coupled receptors (GPCRs) also called heptahelical or seven transmembrane receptors (7TMR). After agonist exposure, these receptors acquire an active conformation, which is recognized by a family of highly specialized GPCR kinases (GRKs). Agonist-driven phosphorylation by GRKs regulates acute receptor desensitization, arrestin recruitment, internalization, post-activation signaling, long-term tolerance and drug addiction. Phosphosite-specific 7TM antibodies are designed to specifically detect agonist-activated GPCRs. In fact, recent work shows that ligand profiling using phosphosite-specific 7TM antibodies provides valuble information on ligand bias beyond that obtained with conventional ß-arrestin recruitment assays. Phosphosite-specific 7TM antibodies are novel tools for GPCR research that can be used to:

  • profile agonist properties of novel GPCR ligands
  • decipher the phosphorylation barcode of GPCRs
  • determine the spatial and temporal dynamics of receptor phosphorylation
  • identify relevant kinases and phosphatases for GPCR phosphorylation and dephosphoryation

Lifecycle3

Schematic representation of the G protein-coupled receptor phosphorylation / dephosphorylation cycle. GRK, G protein-coupled receptor kinase; PKC, protein kinase C; cPP1, catalytic subunit of protein phosphatase 1; R*, activated GPCR; CCP, clathrin-coated pit. 

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Agonist-induced Serine332/Serine334 phosphorylation of the Complement C5a Receptor 1.
pS332/pS334-C5a1 (phospho-Complement C5a...
Serine332/serine334 (S332/S334) is a major phosphorylation site of the C5a1 receptor. The pS332/pS334-C5a1 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S332/S334...
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Agonist-induced Threonine324/Serine327 phosphorylation of the Complement C5a Receptor 1.
pT324/pS327-C5a1 (phospho-Complement C5a...
Threonine324/serine327 (T324/S327) is a major phosphorylation site of the C5a1 receptor. The pT324/pS327-C5a1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. T324/S327...
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Agonist-induced Serine320/Serine321 phosphorylation of the CXC Chemokine Receptor 6
pS320/pS321-CXCR6 (phospho-CXC Chemokine...
Serine320/Serine321 (S320/S321) is a major phosphorylation site of the CXCR6 receptor. The pS320/pS321-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S320/S321...
$ 375.00 *
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Agonist-induced Serine325/Threonine327 phosphorylation of the CXC Chemokine Receptor 6
pS325/pT327-CXCR6 (phospho-CXC Chemokine...
Serine325/Threonine327 (S325/T327) is a major phosphorylation site of the CXCR6 receptor. The pS325/pT327-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S325/T327...
$ 375.00 *
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Agonist-induced Serine329/Serine331 phosphorylation of the CXC Chemokine Receptor 6
pS329/pS331-CXCR6 (phospho-CXC Chemokine...
Serine329/Serine331 (S329/S331) is a major phosphorylation site of the CXCR6 receptor. The pS329/pS331-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S329/S331...
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Agonist-induced Serine338/Threonine342 phosphorylation of the Atypical Chemokine Receptor 4
pS338/pT342-ACKR4 (phospho-Atypical Chemokine...
Serine338/Threonine342 (S338/T342) is major phosphorylation site of the Atypical Chemokine Receptor 4 (ACKR4). The pS338/pT342-ACKR4 antibody detects phosphorylation in response to agonists. S338/ST42 phosphorylation is likely to be...
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pS348/pS350-ACKR2 (phospho-Atypical Chemokine Receptor 2 Antibody)
pS348/pS350-ACKR2 (phospho-Atypical Chemokine...
Serine348/Serine350 (S348/S350) is major phosphorylation site of the Atypical Chemokine Receptor 2 (ACKR2). The pS348/pS350-ACKR2 antibody detects phosphorylation in response to agonists. S348/S350 phosphorylation is likely to be...
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Agonist-induced Serine363/Threonine364 phosphorylation of the Bombesin Receptor 2
pS363/pT364-BB2 (phospho-Bombesin Receptor 2...
Serine363/Threonine364 (S363/T364) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pS363/pT364-BB2 antibody detects phosphorylation in response to agonists. S363/T364 phosphorylation is likely to be involved in...
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Immunohistochemical identification of Glucagon-Like Peptide 1 Receptor in pancreas
GLP1 (IHC-grade), Glucagon-Like Peptide 1...
The GLP1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GLP1 Receptor. The GLP1 antibody can be used to isolate and enrich GLP1 receptors from cell and tissue lysates. It also detects GLP1 in...
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Validation of the FFA2 in transfected HEK293 cells
FFA2 (non-phospho-FFA2 Antibody)
The non-phospho-FFA2 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human FFA2. It can be used to detect total FFA2 receptors in Western blots independent of phosphorylation. The non-phospho-FFA2...
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Immunohistochemical varification of 5-Hydroxytryptamine Receptor 2C antibody in Rat Striatum
5-HT2C (IHC-grade), 5-HT Receptor 2C Antibody
The 5-HT2C receptor antibody is directed against the distal part of the carboxyl-terminal tail of human 5-Hydroxytryptamine Receptor 2C (5-HT2C). The non-phospho-5-HT2C antibody can also be used to isolate and enrich 5-HT2C receptors...
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Immunohistochemical identification of 5-Hydroxytryptamine Receptor 4 in kidney
5-HT4 (IHC-grade), 5-HT Receptor 4 Antibody
The 5-HT4 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human 5-Hydroxytryptamine Receptor 4 (5-HT4). It can be used to detect total 5-HT4 receptors in Western blots independent of...
$ 375.00 *
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Immunohistochemical identification of XCR Chemokine Receptor 1 in pancreas
XCR1 (IHC-grade), XCR Chemokine Receptor 1...
The non-phospho-XCR1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human XCR1. It can be used to detect total XCR1 receptors in Western blots independent of phosphorylation. The non-phospho-XCR1...
$ 375.00 *
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Immunohistochemical identification of Dopamine Receptor 5 in human cortex
D5 (IHC-grade), Dopamine Receptor 5 Antibody
The D5 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human D5. It can be used to detect total D5 receptors in Western blots independent of phosphorylation. The D5 antibody can also be used to...
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Agonist-induced Serine323/Serine324 phosphorylation of the GPR139 Receptor
pS323/pS324-GPR139 (phospho-GPR139 Antibody)
Serine323/Serine324 (S323/S324) is major phosphorylation site of the GPR139 Receptor (GPR139). The pS323/pS324-GPR139 antibody detects phosphorylation in response to agonists. S323/S324 phosphorylation is likely to be involved in...
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Validation of the mouse S1P5 Receptor in transfected HEK293 cells
mS1P5 (non-phospho), Mouse Sphingosine...
The non-phospho-mS1P5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouseS1P5. It can be used to detect total mS1P5 receptors in Western blots independent of phosphorylation. The mS1P5 antibody can...
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21 From 37

For further reading refer to:

Kliewer A, Reinscheid RK, Schulz S. Emerging Paradigms of G Protein-Coupled Receptor Dephosphorylation. Trends Pharmacol Sci. 2017 Jul;38(7):621-636. doi:10.1016/j.tips.2017.04.002. Epub 2017 May 4. Review. PubMed PMID: 28478994.

Miess E, Gondin AB, Yousuf A, Steinborn R, Mösslein N, Yang Y, Göldner M, Ruland JG, Bünemann M, Krasel C, Christie MJ, Halls ML, Schulz S, Canals M. Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid μ-opioid receptor desensitization. Sci Signal. 2018 Jul 17;11(539). pii: eaas9609. doi: 10.1126/scisignal.aas9609. PubMed PMID: 30018083.

Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S. Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects. Nat Commun. 2019 Jan 21;10(1):367. doi: 10.1038/s41467-018-08162-1. PubMed PMID: 30664663; PubMed Central PMCID: PMC6341117.

Mann A, Moulédous L, Froment C, O'Neill PR, Dasgupta P, Günther T, Brunori G, Kieffer BL, Toll L, Bruchas MR, Zaveri NT, Schulz S. Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Sci Signal. 2019 Mar 26;12(574). pii: eaau8072. doi: 10.1126/scisignal.aau8072. PubMed PMID: 30914485; PubMed Central PMCID: PMC6934085.

Saaber F, Schütz D, Miess E, Abe P, Desikan S, Ashok Kumar P, Balk S, Huang K, Beaulieu JM, Schulz S, Stumm R. ACKR3 Regulation of Neuronal Migration Requires ACKR3 Phosphorylation, but Not β-Arrestin. Cell Rep. 2019 Feb 5;26(6):1473-1488.e9. doi: 10.1016/j.celrep.2019.01.049. PubMed PMID: 30726732.

Glück L, Loktev A, Moulédous L, Mollereau C, Law PY, Schulz S. Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5. Biol Psychiatry. 2014 Nov 15;76(10):767-74. doi: 10.1016/j.biopsych.2014.01.021. Epub 2014 Feb 3. PubMed PMID: 24629717; PubMed Central PMCID: PMC4119866.

For further reading refer to: Kliewer A, Reinscheid RK, Schulz S. Emerging Paradigms of G Protein-Coupled Receptor Dephosphorylation. Trends Pharmacol Sci. 2017 Jul;38(7):621-636.... read more »
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For further reading refer to:

Kliewer A, Reinscheid RK, Schulz S. Emerging Paradigms of G Protein-Coupled Receptor Dephosphorylation. Trends Pharmacol Sci. 2017 Jul;38(7):621-636. doi:10.1016/j.tips.2017.04.002. Epub 2017 May 4. Review. PubMed PMID: 28478994.

Miess E, Gondin AB, Yousuf A, Steinborn R, Mösslein N, Yang Y, Göldner M, Ruland JG, Bünemann M, Krasel C, Christie MJ, Halls ML, Schulz S, Canals M. Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid μ-opioid receptor desensitization. Sci Signal. 2018 Jul 17;11(539). pii: eaas9609. doi: 10.1126/scisignal.aas9609. PubMed PMID: 30018083.

Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S. Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects. Nat Commun. 2019 Jan 21;10(1):367. doi: 10.1038/s41467-018-08162-1. PubMed PMID: 30664663; PubMed Central PMCID: PMC6341117.

Mann A, Moulédous L, Froment C, O'Neill PR, Dasgupta P, Günther T, Brunori G, Kieffer BL, Toll L, Bruchas MR, Zaveri NT, Schulz S. Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Sci Signal. 2019 Mar 26;12(574). pii: eaau8072. doi: 10.1126/scisignal.aau8072. PubMed PMID: 30914485; PubMed Central PMCID: PMC6934085.

Saaber F, Schütz D, Miess E, Abe P, Desikan S, Ashok Kumar P, Balk S, Huang K, Beaulieu JM, Schulz S, Stumm R. ACKR3 Regulation of Neuronal Migration Requires ACKR3 Phosphorylation, but Not β-Arrestin. Cell Rep. 2019 Feb 5;26(6):1473-1488.e9. doi: 10.1016/j.celrep.2019.01.049. PubMed PMID: 30726732.

Glück L, Loktev A, Moulédous L, Mollereau C, Law PY, Schulz S. Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5. Biol Psychiatry. 2014 Nov 15;76(10):767-74. doi: 10.1016/j.biopsych.2014.01.021. Epub 2014 Feb 3. PubMed PMID: 24629717; PubMed Central PMCID: PMC4119866.

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