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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 Serine433/Serine435 phosphorylation of GIPR
pS433/pS435-GIPR (phospho-Gastric Inhibitory...
Serine433/Serine435 (S433/S435) is major phosphorylation site of human GIP receptor. The pS433/pS435-GIPR antibody detects phosphorylation in response to agonists. S433/S435 phosphorylation is likely to be involved in efficient ligand...
£ 335.00 *
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Immunohistochemical control of anti-NPS (Neuropeptide S) antibody in mouse coronal sections
NPS (IHC-grade), Neuropeptide S Antibody
The NPS antibody is directed against human Neuropeptide S. The NPS antibody can be used to detect Neuropeptide S in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry.
£ 335.00 *
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Immunohistochemical identification of Nociceptin/Orphanin FQ in mouse dorsal horn
N/OFQ (IHC-grade), Nociceptin/Orphanin FQ Antibody
The N/OFQ receptor antibody is directed against human Nociceptin/Orphanin FQ. The N/OFQ antibody can be used to detect N/OFQ in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry.
£ 335.00 *
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NEW
Immunohistochemical identification of G Protein-coupled Receptor 84 in lymph node
GPR84 (IHC-grade), G Protein-Coupled Receptor...
The GPR84 antibody is directed against the distal end of the carboxyl-terminal tail of human GRP84. It can be used to detect total GPR84 receptors in Western blots independent of phosphorylation. The GPR84 antibody can also be used to...
£ 335.00 *
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Agonist-induced Serine335/Serine337 phosphorylation of the Sphingosine 1-Phosphate Receptor 3
pS335/pS337-S1P3 (phospho-Sphingosine...
Serine335/Serine337 (S335/S337) is major phosphorylation site of the Sphingosine 1-Phosphate Receptor 3 (S1P3). The pS335/pS337-S1P3 antibody detects phosphorylation in response to agonists. S335/S337 phosphorylation is likely to be...
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NEW
Immunohistochemical identification of G Protein-coupled Receptor 82 in hippocampus
GPR82 (IHC-grade), G Protein-Coupled Receptor...
The GPR82 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP82. It can be used to detect total GPR82 receptors in Western blots independent of phosphorylation. The GPR82 antibody can...
£ 335.00 *
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Immunohistochemical identification of G Protein-coupled Receptor 65 in small intestine
GPR65 (IHC-grade), G Protein-Coupled Receptor...
The GPR65 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP65. It can be used to detect total GPR65 receptors in Western blots independent of phosphorylation. The GPR65 antibody can...
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Immunohistochemical identification of G Protein-coupled Receptor 61 in cortex
GPR61 (IHC-grade), G Protein-Coupled Receptor...
The GPR61 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP61. It can be used to detect total GPR61 receptors in Western blots independent of phosphorylation. The GPR61 antibody can...
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Immunohistochemical identification of GPR3 Receptor in Cortex
GPR3 (IHC-grade), G Protein-Coupled Receptor 3...
The GPR3 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP3. It can be used to detect total GPR3 receptors in Western blots independent of phosphorylation. The GPR3 antibody can also be...
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Agonist-induced Serine331/Threonine332 phosphorylation of the Angiotensin Receptor 1
pS331/pT332-AT1 (phospho-Angiotensin Receptor 1...
Serine331/Threonine332 (S331/T332) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS331/pT332-AT1 antibody detects phosphorylation in response to agonists. S331/T332 phosphorylation is likely to be involved in...
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Immunohistochemical identification of G Protein-coupled Receptor 17 in oligodendrocytes.
GPR17 (IHC-grade), G Protein-Coupled Receptor...
The GPR17 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP17. It can be used to detect total GPR17 receptors in Western blots independent of phosphorylation. The GPR17 antibody can...
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SAMPLE PACK
Agonist-induced Serine331/Threonine332 phosphorylation of the Angiotensin Receptor 1
AT1 Sample Pack (phospho- and...
AT1 Sample Pack consisting of all four available phospho- and non-phospho-AT1 Antibodies 7 x 20 µL trial size each.
£ 300.00 *
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Immunohistochemical identification of GPR32 Receptor in Small Intestine
GPR32 (IHC-grade), G Protein-Coupled Receptor...
The GPR32 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP32. It can be used to detect total GPR32 receptors in Western blots independent of phosphorylation. The GPR32 antibody can...
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NEW
Immunohistochemical identification of GPR27 Receptor in small intestine
GPR27 (IHC-grade), G Protein-Coupled Receptor...
The GPR27 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP27. It can be used to detect total GPR27 receptors in Western blots independent of phosphorylation. The GPR27 antibody can...
£ 335.00 *
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NEW
Immunohistochemical identification of GPR12 Receptor in kidney
GPR12 (IHC-grade), G Protein-Coupled Receptor...
The GPR12 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP12. It can be used to detect total GPR12 receptors in Western blots independent of phosphorylation. The GPR12 antibody can...
£ 335.00 *
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NEW
Immunohistochemical identification of GPR25 Receptor in small intestine
GPR25 (IHC-grade), G Protein-Coupled Receptor...
The GPR25 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP25. It can be used to detect total GPR25 receptors in Western blots independent of phosphorylation. The GPR25 antibody can...
£ 335.00 *
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15 From 43

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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