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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 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...
375.00 € *
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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.
375.00 € *
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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.
375.00 € *
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Immunohistochemical Identification of Agonist-induced Serine425 phosphorylation of the Cannabinoid Receptor 1 in mouse brain
pS425-CB1 (IHC-grade phospho-Cannabinoid...
Serine425 (S425) is major phosphorylation site of the Cannabinoid Receptor 1 (CB1). The pS425-CB1 antibody detects phosphorylation in response to agonists. S425 phosphorylation is likely to be involved in efficient ligand sequestration...
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Immunohistochemical Identification of Serine296/Serine297 phosphorylation of the FFA Receptor 2 in mouse white adipose tissue and peyer's patches.
pS296/pS297-FFA2 (IHC-grade phospho-FFA2 Antibody)
Serine296/Serine297 (S296/S297) is major phosphorylation site of the FFA Receptor 2 (FFA2). The pS296/pS297-FFA2 antibody detects constitutive phosphorylation of FFA2.
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Immunohistochemical Identification of Threonine306/Threonine310 phosphorylation of the FFA Receptor 2 in mouse neuroendocrine cells and peyer's patches.
pT306/pT310-FFA2 (IHC grade phospho-FFA2 Antibody)
Threonine306/Threonine310 (T306/T310) is major phosphorylation site of the FFA 2 Receptor (FFA2). The pT306/pT310-FFA2 antibody detects phosphorylation in response to agonists. T306/T310 phosphorylation is likely to be involved in...
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Immunohistochemical identification of Dopamine Receptor 1 and Dopamine Receptor 2 in striatum
D2 (IHC-grade), Dopamine Receptor 2 Antibody
The D2 receptor antibody is directed against the third intracellular loop of mouse, rat and human D2 dopamine receptor. It detects both the long and short form of D2. It can be used to detect total D2 receptors in Western blots...
375.00 € *
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Immunohistochemical identification of GPR6 Receptor in small intestine
GPR6 (IHC-grade), G Protein-Coupled Receptor 6...
The GPR6 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP6. It can be used to detect total GPR6receptors in Western blots independent of phosphorylation. The GPR6 antibody can also be...
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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...
375.00 € *
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Immunohistochemical identification of GPR15 Receptor in kidney
GPR15 (IHC-grade), G Protein-Coupled Receptor...
The GPR15 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP15. It can be used to detect total GPR15 receptors in Western blots independent of phosphorylation. The GPR15 antibody can...
375.00 € *
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Immunohistochemical identification of GPR22 Receptor in Pancreas
GPR22 (IHC-grade), G Protein-Coupled Receptor...
The GPR22 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP22. It can be used to detect total GPR22 receptors in Western blots independent of phosphorylation. The GPR22 antibody can...
375.00 € *
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GPR25 (IHC-grade), G Protein-Coupled Receptor 25 Antibody
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...
375.00 € *
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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...
375.00 € *
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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...
375.00 € *
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Immunohistochemical identification of SUCNR1 Receptor in Pancreas
SUCNR1/GPR91 (IHC-grade), Succinate Receptor...
The SUCNR1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SUCNR1. It can be used to detect total SUCNR1 receptors in Western blots independent of phosphorylation. The SUCNR1 antibody can also...
375.00 € *
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Immunohistochemical identification of GPR39 Receptor in Small Intestine
GPR39 (IHC-grade), G Protein-Coupled Receptor...
The GPR39 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP39. It can be used to detect total GPR39 receptors in Western blots independent of phosphorylation. The GPR39 antibody can...
375.00 € *
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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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