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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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SCTR (non-phospho) Scretin Receptor Antibody
SCTR (non-phospho) Scretin Receptor Antibody
The non-phospho SCTR receptor antibody is directed against the distal end of the carboxyl-terminal tail human SCTR receptor. It can be used to detect total SCTR receptors in Western blots independent of phosphorylation. It can also be...
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QRFPR (non-phospho) QRFP Receptor Antibody
QRFPR (non-phospho) QRFP Receptor Antibody
The non-phospho QRFP receptor antibody is directed against the distal end of the carboxyl-terminal tail human QRFP receptor. It can be used to detect total QRFP receptors in Western blots independent of phosphorylation. It can also be...
375.00 € *
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OX2 (non-phospho) Orexin Receptor 2 Antibody
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...
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NPY1 (non-phospho) Neuropeptide Y Receptor 1 Antibody
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...
375.00 € *
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NPY2 (non-phospho) Neuropeptide Y Receptor 2 Antibody
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...
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MT1 (non-phospho) Melatonin Receptor 1 Antibody
MT1 (non-phospho) Melatonin Receptor 1 Antibody
The non-phospho MT1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human MT1 receptor. It can be used to detect total MT1 receptors in Western blots independent of phosphorylation. It can also be used...
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MCH2 (non-phospho) Melanin-Concentrating Hormone Receptor 2 Antibody
MCH2 (non-phospho) Melanin-Concentrating...
The non-phospho MCH2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human MCH2 receptor. It can be used to detect total MCH2 receptors in Western blots independent of phosphorylation. It can also be...
375.00 € *
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HCA1 (non-phospho) Hydroxycarboxylic Acid Receptor 1 Antibody
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...
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pT442/pS443-GIPR (phospho-Gastric Inhibitory Polypeptide Receptor Antibody)
pT442/pS443-GIPR (phospho-Gastric Inhibitory...
Threonine442/Serine443 (T442/S443) is major phosphorylation site of human GIP receptor. The pT442/pS443-GIPR antibody detects phosphorylation in response to agonists. T442/S443 phosphorylation is likely to be involved in efficient ligand...
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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...
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CCR5 (GP-non-phospho) Chemokine Receptor 5 Antibody, Guinea Pig
CCR5 (GP-non-phospho) Chemokine Receptor 5...
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...
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CCR5 (non-phospho) Chemokine Receptor 5 Antibody
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...
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Immunohistochemical identification of the Formylpeptide Receptor 2 in striatum
FPR2 (IHC-grade), Formylpeptide Receptor 2...
The FPR2 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human FPR2. It can be used to detect total FPR2 receptors in Western blots independent of phosphorylation. The FPR2 antibody can also be...
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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.
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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...
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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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