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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 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...
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Immunohistochemical identification of CC Chemokine Receptor 10 in kidney
CCR10 (IHC-grade) 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...
CHF400.00 *
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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...
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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...
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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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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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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...
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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...
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Immunohistochemical identification of Orexin Receptor 1 in pancreas
OX1 (IHC-grade) Orexin Receptor 1 Antibody
The non-phospho OX1 receptor antibody is directed against the distal end of the carboxyl-terminal tail human OX1 receptor. It can be used to detect total OX1 receptors in Western blots independent of phosphorylation. It can also be used...
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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...
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Immunohistochemical identification of QRFP Receptor in heart
QRFPR (IHC-grade), 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...
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Immunohistochemical identification of Secretin Receptor in human cortex
SCTR (IHC-grade), Secretin 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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Immunohistochemical identification of TP Tromboxane Receptor in pancreas
TP (IHC-grade), 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...
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Immunohistochemical identification of FP Prostanoid Receptor in pancreas
FP (IHC-grade), FP Prostanoid Receptor Antibody
The non-phospho-FP Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human FP. It can be used to detect total FP receptors in Western blots independent of phosphorylation. The non-phospho-FP antibody...
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Immunohistochemical identification of DP1 Prostanoid receptor 1 in kidney
DP1 (IHC-grade), DP1 Prostanoid Receptor Antibody
The non-phospho-DP1 Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human DP1. It can be used to detect total DP1 receptors in Western blots independent of phosphorylation. The non-phospho-DP1...
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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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