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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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Validation of the CC Chemokine Receptor 10 in transfected HEK293 cells
CCR10 (non-phospho) Chemokine Receptor 10 Antibody
The non-phospho-CCR10 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR10. It can be used to detect total CCR10 receptors in Western blots independent of phosphorylation. The CCR10 antibody...
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Immunohistochemical identification of CC Chemokine Receptor 6 in pancreas
CCR6 (IHC-grade) Chemokine Receptor 6 Antibody
The non-phospho-CCR6 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR6. It can be used to detect total CCR6 receptors in Western blots independent of phosphorylation. The CCR6 antibody can...
375.00 € *
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Validation of the CC Chemokine Receptor 6 in transfected HEK293 cells
CCR6 (non-phospho) Chemokine Receptor 6 Antibody
The non-phospho-CCR6 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR6. It can be used to detect total CCR6 receptors in Western blots independent of phosphorylation. The CCR6 antibody can...
375.00 € *
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Validation of the IP Prostacyclin Receptor in transfected HEK293 cells
IP (non-phospho), IP Prostacyclin Receptor...
The non-phospho-IP Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human IP. It can be used to detect total IP receptors in Western blots independent of phosphorylation. The non-phospho-IP antibody...
375.00 € *
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Validation of the TP Tromboxane Receptor in transfected HEK293 cells
TP (non-phospho), TP Thromboxane Receptor Antibody
The non-phospho-TP Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human TP. It can be used to detect total TP receptors in Western blots independent of phosphorylation. The non-phospho-TP antibody...
375.00 € *
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Validation of the Vasopressin Receptor 1A in transfected HEK293 cells
V1A (non-phospho), Vasopressin Receptor 1A...
The non-phospho-V1A Receptor 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 non-phospho-V1A...
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Agonist-induced Threonine315/Threonine316 phosphorylation of the M4 Muscarinic Acetylcholine Receptor
pT315/pT316-M4 (phospho-M4 Muscarinic...
Threonine315/Threonine316 is a major phosphorylation site of the M4 Muscarinic Acetylcholine Receptor. The pT315/pT316-M4 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. T315/T316...
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Agonist-induced Serine326/Threonine327/Serine328 phosphorylation of the Hydroxycarboxylic Acid Receptor 2
pS326/pT327/pS328-HCA2...
Serine326/Threonine327/Serine328 (S326/T327/S328) is major phosphorylation site of the Hydroxycarboxylic Acid Receptor 2 (HCA2). The pS326/pT327/pS328-HCA2 antibody detects phosphorylation in response to agonists. S326/T327/S328...
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Agonist-induced Serine347 phosphorylation of the mouse Sphingosine 1-Phosphate Receptor 5
pS347-mS1P5 (phospho-mouse-Sphingosine...
Serine347 (S347) is major phosphorylation site of the mouse Sphingosine 1-Phosphate Receptor 5 (S1P5). The pS347-mS1P5 antibody detects phosphorylation in response to agonists. S347 phosphorylation is likely to be involved in efficient...
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Agonist-induced Serine362/Serine363/Serine364 phosphorylation of the mouse Sphingosine 1-Phosphate Receptor 5
pS362/pS363/pS364-mS1P5...
Serine362/Serine363/Serine364 (S362/S363/S364) is major phosphorylation site of the mouse Sphingosine 1-Phosphate Receptor 5 (mS1P5). The pS362/pS363/pS364-mS1P5 antibody detects phosphorylation in response to agonists. S362/S363/S364...
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Immunohistochemical identification of Vasopressin Receptor 1A in pancreas
V1A (IHC-grade), Vasopressin Receptor 1A Antibody
The non-phospho-V1A Receptor 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 non-phospho-V1A...
375.00 € *
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Agonist-induced Serine445 phosphorylation of Glucagon Receptor
pS445-GCGR (phospho-Glucagon Receptor Antibody)
Serine445 (S445) is major phosphorylation site of human GCGR receptor. The pS445-GCGR antibody detects phosphorylation in response to agonists. S445 phosphorylation is likely to be involved in efficient ligand sequestration by the...
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Agonist-induced Serine349/Threonine350/Threonine351 phosphorylation of the Sphingosine 1-Phosphate Receptor 4
pS349/pT350/pT351-S1P4 (phospho-Sphingosine...
Serine349/Threonin350/Threonine351 (S349/T350/T351) is major phosphorylation site of the Sphingosine 1-Phosphate Receptor 4 (S1P4). The pS349/pT350/pT351-S1P4 antibody detects phosphorylation in response to agonists. S349/T350/T351...
375.00 € *
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Agonist-induced Serine396/Threonine phosphorylation of the Neuromedin U Receptor 1
pS396/pT397-NMU1 (phospho-Neuromedin U Receptor...
Serine396/Threonine397 is major phosphorylation site of the Neuromedin U Receptor 1 (NMU1). The pS396/pT397-NMU1 antibody detects phosphorylation in response to agonists. S396/pT397 phosphorylation is likely to be involved in efficient...
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Validation of the CC Chemokine Receptor 5 in transfected HEK293 cells
CCR5 (non-phospho) Chemokine Receptor 5 Antibody
The non-phospho-CCR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR5. It can be used to detect total CCR5 receptors in Western blots independent of phosphorylation. The CCR5 antibody can...
375.00 € *
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Immunohistochemical identification of Serine298/Serine300 phosphorylation of M4 Receptor in striatum
pS298/pS300-M4 (IHC-grade phospho-M4 Muscarinic...
Serine298/Serine300 is a major phosphorylation site of the M4 Muscarinic Acetylcholine Receptor. The pS298/pS300-M4 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. S298/S300...
550.00 € *
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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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