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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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GPR37L1 (IHC-Grade), G protein-coupled Receptor 37L1 Antibody
GPR37L1 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR37L1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR37L1. It can be used to detect total GPR37L1 receptors in Western blots independent of phosphorylation. The GPR37L1...
£ 335.00 *
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NEW
Validation of the GPR68 Receptor in transfected HEK293 cells.
GPR68 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR68 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR68. It can be used to detect total GPR68 receptors in Western blots independent of phosphorylation. The GPR68 antibody...
£ 335.00 *
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GPR68 (IHC-Grade), G protein-coupled Receptor 68 Antibody
GPR68 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR68 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR68. It can be used to detect total GPR68 receptors in Western blots independent of phosphorylation. The GPR68 antibody...
£ 335.00 *
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Validation of the GPBA Receptor in transfected HEK293 cells.
GPBA (non-phospho), Bile Acid Receptor Antibody
The non-phospho-GPBA receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPBA. It can be used to detect total GPBA receptors in Western blots independent of phosphorylation. The GPBA antibody can...
£ 335.00 *
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GPBA (IHC-Grade), Bile Acid Receptor Antibody
GPBA (IHC-Grade), Bile Acid Receptor Antibody
The non-phospho-GPBA receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPBA. It can be used to detect total GPBA receptors in Western blots independent of phosphorylation. The GPBA antibody can...
£ 335.00 *
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Rabbit Monoclonal
KD-Validated
NEW
SST3 [UMB5] (RM-IHC-grade), Somatostatin Receptor 3 Antibody, Rabbit Monoclonal
SST3 [UMB5] (RM-IHC-grade), Somatostatin...
The SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Somatostatin Receptor 3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The SST3...
£ 495.00 *
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Rabbit Monoclonal
NEW
V1A [UMB21] (RM-IHC-Grade-Vasopressin Receptor 1A Antibody), Rabbit Monoclonal
V1A [UMB21] (RM-IHC-Grade-Vasopressin Receptor...
The non-phospho-V1A antibody is directed against the distal end of the carboxyl-terminal tail of human V1A. It can be used to detect total V1A receptors in Western blots independent of phosphorylation. The V1A antibody can also be used...
£ 495.00 *
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Rabbit Monoclonal
NEW
BB2 [UMB17] (RM-non-phospho-Bombesin Receptor 2 Antibody), Rabbit Monoclonal
BB2 [UMB17] (RM-non-phospho-Bombesin Receptor 2...
The non-phospho-BB2 antibody is directed against the distal end of the carboxyl-terminal tail of human BB2. It can be used to detect total BB2 receptors in Western blots independent of phosphorylation. The BB2 antibody can also be used...
£ 495.00 *
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Rabbit Monoclonal
NEW
Validation of the Calcitonin Receptor in transfected HEK293 cells
CT [UMB25] (RM-non-phospho-Calcitonin Receptor...
The non-phospho-CT antibody is directed against the distal end of the carboxyl-terminal tail of human CT. It can be used to detect total CT receptors in Western blots independent of phosphorylation. The CT antibody can also be used to...
£ 495.00 *
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Rabbit Monoclonal
NEW
BB2 [UMB17] (RM-IHC-Grade-Bombesin Receptor 2 Antibody), Rabbit Monoclonal
BB2 [UMB17] (RM-IHC-Grade-Bombesin Receptor 2...
The non-phospho-BB2 antibody is directed against the distal end of the carboxyl-terminal tail of human BB2. It can be used to detect total BB2 receptors in Western blots independent of phosphorylation. The BB2 antibody can also be used...
£ 495.00 *
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Rabbit Monoclonal
NEW
B2 [UMB12] (RM-IHC-Grade-Bradykinin Receptor 2 Antibody), Rabbit Monoclonal
B2 [UMB12] (RM-IHC-Grade-Bradykinin Receptor 2...
The non-phospho-B2 Bradykinin Receptor antibody is directed against the distal end of the carboxyl-terminal tail of human B2. It can be used to detect total B2 receptors in Western blots independent of phosphorylation. The B2 antibody...
£ 495.00 *
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Rabbit Monoclonal
NEW
MCH1 [UMB20] (RM-IHC-Grade-Melanin-Concentrating Hormone Receptor 1 Antibody), Rabbit Monoclonal
MCH1 [UMB20]...
The non-phospho-MCH1 antibody is directed against the distal end of the carboxyl-terminal tail of human MCH1. It can be used to detect total MCH1 receptors in Western blots independent of phosphorylation. The MCH1 antibody can also be...
£ 495.00 *
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Validation of the GPR161 Receptor in transfected HEK293 cells
GPR161 (non-phospho), G protein-coupled...
The non-phospho-GPR161 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR161. It can be used to detect total GPR161 receptors in Western blots independent of phosphorylation. The GPR161...
£ 335.00 *
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Immunohistochemical identification of Threonine344/Serine347 phosphorylation of NK1 Receptor in striatum
pT344/pS347-NK1 (IHC-grade phospho-Tachykinin...
Threonine344/Serine347 (T344/S347) is a major phosphorylation site of the NK1 receptor. The pT344/pS347-NK1 antibody detects phosphorylation in response to high-efficacy agonists. T344/S347 phosphorylation is a key regulator of NK1...
£ 550.00 *
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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...
£ 335.00 *
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Agonist-induced Threonine315 phosphorylation of the GPR139 Receptor
pT315-GPR139 (phospho-GPR139 Antibody)
Threonine315 (T315) is major phosphorylation site of the GPR139 Receptor (GPR139). The pT315-GPR139 antibody detects phosphorylation in response to agonists. T315 phosphorylation is likely to be involved in efficient ligand sequestration.
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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.

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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