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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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Validation of the Glucagon-Like Peptide 2 Receptor in transfected HEK293 cells
GLP2 (non-phospho) Glucagon-Like Peptide 2...
The non-phospho GLP2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human GLP2 receptor. It can be used to detect total GLP2 receptors in Western blots independent of phosphorylation. It can also be...
$ 375.00 *
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Immunohistochemical identification of Glucagon-Like Peptide 2 Receptor in enteric ganglion
GLP2 (IHC-grade), Glucagon-Like Peptide 2...
The non-phospho GLP2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human GLP2 receptor. It can be used to detect total GLP2 receptors in Western blots independent of phosphorylation. It can also be...
$ 375.00 *
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Validation of the Glucagon Receptor in transfected HEK293 cells
GCGR (non-phospho) Glucagon Receptor Antibody
The non-phospho GCGR antibody is directed against the distal end of the carboxyl-terminal tail of human GCGR. It can be used to detect total GCGR receptors in Western blots independent of phosphorylation. It can also be used to isolate...
$ 375.00 *
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Validation of the Gastric Inhibitory Polypeptide Receptor in transfected HEK293 cells
GIPR (non-phospho) Gastric Inhibitory...
The non-phospho GIPR antibody is directed against the distal end of the carboxyl-terminal tail human GIPR. It can be used to detect total GIPR receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
$ 375.00 *
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pS331/pT332-LPA2 (phospho-Lysophosphatidic Acid Receptor 2 Antibody)
pS331/pT332-LPA2 (phospho-Lysophosphatidic Acid...
Serine331/Threonine332 (S331/T332) is major phosphorylation site of the Lysophosphatidic Acid Receptor 2 (LPA2). pS331/pT332-LPA2 antibody detects phosphorylation in response to agonists. S331/T332 phosphorylation is likely to be...
$ 375.00 *
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pS326/pS328-AT1 (phospho-Angiotensin Receptor 1 Antibody)
pS326/pS328-AT1 (phospho-Angiotensin Receptor 1...
Serine326/Serine328 (S326/S328) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS326/pS328-AT1 antibody detects phosphorylation in response to agonists. S326/S328 phosphorylation is likely to be involved in...
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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...
$ 375.00 *
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Validation of the CC Chemokine Receptor 10 in transfected HEK293 cells
CCR10 (non-phospho) 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...
$ 375.00 *
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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...
$ 375.00 *
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Validation of the CC Chemokine Receptor 6 in transfected HEK293 cells
CCR6 (non-phospho) 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...
$ 375.00 *
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Validation of the CC Chemokine Receptor 5 in transfected HEK293 cells
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...
$ 375.00 *
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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...
$ 375.00 *
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Validation of the TP Tromboxane Receptor in transfected HEK293 cells
TP (non-phospho), 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...
$ 375.00 *
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Immunohistochemical identification of FP Prostanoid Receptor in rat cortex
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...
$ 375.00 *
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Validation of the FP Prostanoid Receptor in transfected HEK293 cells
FP (non-phospho), 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...
$ 375.00 *
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Validation of the IP Prostacyclin Receptor in transfected HEK293 cells
IP (non-phospho), IP Prostacyclin Receptor...
The non-phospho-IP Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human IP. It can be used to detect total IP receptors in Western blots independent of phosphorylation. The non-phospho-IP antibody...
$ 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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