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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...
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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...
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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...
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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...
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FP (IHC-grade), FP Prostanoid Receptor Antibody
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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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...
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PAR2 (IHC-grade), Proteinase-Activated Receptor 2 Antibody
PAR2 (IHC-grade), Proteinase-Activated Receptor...
The PAR2 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human PAR2. It can be used to detect total PAR2 receptors in Western blots independent of phosphorylation. The PAR2 antibody can also be...
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Validation of the Vasopressin Receptor 1B in transfected HEK293 cells.
V1B (non-phospho), Vasopressin Receptor 1B...
The non-phospho-V1B Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human V1B. It can be used to detect total V1B receptors in Western blots independent of phosphorylation. The non-phospho-V1B...
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Immunohistochemical identification of Vasopressin Receptor 1B in kidney
V1B (IHC-grade), Vasopressin Receptor 1B Antibody
The non-phospho-V1B Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human V1B. It can be used to detect total V1B receptors in Western blots independent of phosphorylation. The non-phospho-V1B...
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Validation of the Complement C3a Receptor 1 in transfected HEK293 cells
C3a (non-phospho), Complement C3a Receptor...
The non-phospho-C3a receptor antibody is directed against the distal end of the carboxyl-terminal tail of human C3a. It can be used to detect total C3a receptors in Western blots independent of phosphorylation. The non-phospho-C3a...
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C3a (IHC-grade), Complement C3a Receptor Antibody
C3a (IHC-grade), Complement C3a Receptor Antibody
The non-phospho-C3a receptor antibody is directed against the distal end of the carboxyl-terminal tail of human C3a. It can be used to detect total C3a receptors in Western blots independent of phosphorylation. The non-phospho-C3a...
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Validation of the Secretin Receptor in transfected HEK293 cells
SCTR (non-phospho) 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 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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Validation of the P2Y Purinoceptor 4 in transfected HEK293 cells
P2Y4 (non-phospho), P2Y Purinoceptor 4 Antibody
The non-phospho-P2Y4 Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human P2Y4. It can be used to detect total P2Y4 receptors in Western blots independent of phosphorylation. The non-phospho-P2Y4...
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Immunohistochemical identification of P2Y Purinoceptor 4 in pancreas
P2Y4 (IHC-grade), P2Y Purinoceptor 4 Antibody
The non-phospho-P2Y4 Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human P2Y4. It can be used to detect total P2Y4 receptors in Western blots independent of phosphorylation. The non-phospho-P2Y4...
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Validation of the Orexin Receptor 2 in transfected HEK293 cells
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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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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