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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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Immunohistochemical identification of the Cannabinoid Receptor 1 in human cortex
CB1 (IHC-grade), Cannabinoid Receptor 1 Antibody
The non-phospho-CB1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB1. It can be used to detect total CB1 receptors in Western blots independent of phosphorylation. The CB1 antibody can also...
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Immunohistochemical identification of Calcitonin Receptor-Like Receptor in mouse brain
CALCR (IHC-grade) Calcitonin Receptor-Like...
The non-phospho-CALCR receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CALCR. It can be used to detect total CALCR receptors in Western blots independent of phosphorylation. The CALCR antibody...
£ 335.00 *
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Immunohistochemical identification of Vasopressin Receptor 1B in kidney
V1B (IHC-grade), Vasopressin Receptor 1B Antibody
The non-phospho-V1B Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human V1B. It can be used to detect total V1B receptors in Western blots independent of phosphorylation. The non-phospho-V1B...
£ 335.00 *
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Validation of the Vasopressin Receptor 1B in transfected HEK293 cells.
V1B (non-phospho), Vasopressin Receptor 1B...
The non-phospho-V1B Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human V1B. It can be used to detect total V1B receptors in Western blots independent of phosphorylation. The non-phospho-V1B...
£ 335.00 *
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Validation of the P2Y Purinoceptor 4 in transfected HEK293 cells
P2Y4 (non-phospho), P2Y Purinoceptor 4 Antibody
The non-phospho-P2Y4 Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human P2Y4. It can be used to detect total P2Y4 receptors in Western blots independent of phosphorylation. The non-phospho-P2Y4...
£ 335.00 *
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Immunohistochemical identification of P2Y Purinoceptor 4 in pancreas
P2Y4 (IHC-grade), P2Y Purinoceptor 4 Antibody
The non-phospho-P2Y4 Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human P2Y4. It can be used to detect total P2Y4 receptors in Western blots independent of phosphorylation. The non-phospho-P2Y4...
£ 335.00 *
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Validation of the Orexin Receptor 2 in transfected HEK293 cells
OX2 (non-phospho) Orexin Receptor 2 Antibody
The non-phospho OX2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human OX2 receptor. It can be used to detect total OX2 receptors in Western blots independent of phosphorylation. It can also be used...
£ 335.00 *
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Immunohistochemical identification of Orexin Receptor 2 in pancreas
OX2 (IHC-grade) Orexin Receptor 2 Antibody
The non-phospho OX2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human OX2 receptor. It can be used to detect total OX2 receptors in Western blots independent of phosphorylation. It can also be used...
£ 335.00 *
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Immunohistochemical identification of Neuropeptide Y Receptor 1 in mouse hippocampus
NPY1 (IHC-grade), Neuropeptide Y Receptor 1...
The non-phospho NPY1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human NPY1 receptor. It can be used to detect total NPY1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Validation of the Neuropeptide Y Receptor 1 in transfected HEK293 cells
NPY1 (non-phospho) Neuropeptide Y Receptor 1...
The non-phospho NPY1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human NPY1 receptor. It can be used to detect total NPY1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Immunohistochemical identification of Neuropeptide Y Receptor 2 in human cortex
NPY2 (IHC-grade), Neuropeptide Y Receptor 2...
The non-phospho NPY2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human NPY2 receptor. It can be used to detect total NPY2 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Validation of the Neuropeptide Y Receptor 2 in transfected HEK293 cells
NPY2 (non-phospho) Neuropeptide Y Receptor 2...
The non-phospho NPY2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human NPY2 receptor. It can be used to detect total NPY2 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Validation of the Melanin-Concentrating Hormone Receptor 1 in transfected HEK293 cells
MCH1 (non-phospho) Melanin-Concentrating...
The non-phospho MCH1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human MCH1 receptor. It can be used to detect total MCH1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Immunohistochemical identification of Melanin-Concentrating Hormone Receptor 1 in pancreas
MCH1 (IHC-grade) Melanin-Concentrating Hormone...
The non-phospho MCH1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human MCH1 receptor. It can be used to detect total MCH1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Immunohistochemical identification of the Hydroxycarboxylic Acid Receptor 1 in pancreas
HCA1 (IHC-grade), Hydroxycarboxylic Acid...
The non-phospho HCA1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human HCA1 receptor. It can be used to detect total HCA1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Validation of the Hydroxycarboxylic Acid Receptor 1 in transfected HEK293 cells
HCA1 (non-phospho) Hydroxycarboxylic Acid...
The non-phospho HCA1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human HCA1 receptor. It can be used to detect total HCA1 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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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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Premium Phosphosite-Specific 7TM Antibodies

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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