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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 MRGPRX2 Receptor in transfected HEK293 cells
MRGPRX2 (non-phospho), MRGPRX2 Mas-related...
The non-phospho-MRGPRX2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human MRGPRX2. It can be used to detect total MRGPRX2 receptors in Western blots independent of phosphorylation. The MRGPRX2...
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NEW
Immunohistochemical identification of Proteinase-Activated Receptor 4 in Small Intestine
PAR4 (IHC-Grade), Proteinase-Activated Receptor...
The non-phospho-PAR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 4. It can be used to detect total PAR4 receptors in Western blots independent of...
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NEW
Validation of the Proteinase-Activated Receptor 4 in transfected HEK293 cells
PAR4 (non-phospho), Proteinase-Activated...
The non-phospho-PAR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 4. It can be used to detect total PAR4 receptors in Western blots independent of...
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NEW
Validation of the GPR65 Receptor in transfected HEK293 cells
GPR65 (non-phospho), G protein-coupled...
The non-phospho-GPR65 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR65. It can be used to detect total GPR65 receptors in Western blots independent of phosphorylation. The GPR65 antibody...
375.00 € *
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NEW
Validation of the GPR25 Receptor in transfected HEK293 cells
GPR25 (non-phospho), G protein-coupled...
The non-phospho-GPR25 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR25. It can be used to detect total GPR25 receptors in Western blots independent of phosphorylation. The GPR25 antibody...
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NEW
Validation of the GPR61 Receptor in transfected HEK293 cells
GPR61 (non-phospho), G protein-coupled...
The non-phospho-GPR61 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR61. It can be used to detect total GPR61 receptors in Western blots independent of phosphorylation. The GPR61 antibody...
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Validation of the GPR22 Receptor in transfected HEK293 cells
GPR22 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR22 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR22. It can be used to detect total GPR22 receptors in Western blots independent of phosphorylation. The GPR22 antibody...
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NEW
Validation of the GPR3 Receptor in transfected HEK293 cells
GPR3 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR3. It can be used to detect total GPR3 receptors in Western blots independent of phosphorylation. The GPR3 antibody can...
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Validation of the Atypical Chemokine Receptor 3 in transfected HEK293 cells
ACKR3 (GP-non-phos, C-Term), Atypical Chemokine...
The non-phospho-ACKR3 receptor antibody is directed against the carboxyl-terminal tail of mouse, rat and human ACKR3. It can be used to detect total ACKR3 receptors in Western blots independent of phosphorylation. The non-phospho-ACKR3...
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pS350/pT352-ACKR3 (phospho-Atypical Chemokine Receptor 3 Antibody)
pS350/pT352-ACKR3 (phospho-Atypical Chemokine...
Serine350/Threonine352 (S350/T352) is major phosphorylation site of the Atypical Chemokine Receptor 3 (ACKR3, previously called CXCR7). The pS350/pT352-ACKR3 antibody detects phosphorylation in response to agonists and after PKC...
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Validation of the Formylpeptide Receptor 2 in transfected HEK293 cells
FPR2 (GP-non-phospho), Formylpeptide Receptor 2...
The FPR2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Formylpeptide Receptor 2. It can be used to detect total FPR2 receptors in Western blots independent of phosphorylation. The FPR2...
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Agonist-induced Threonine335 phosphorylation of FPR2 Receptor
pT335-FPR2 (phospho-Formylpeptide Receptor 2...
Threonine335 (T335) is a major phosphorylation site of the FPR2 receptor. The pT335-FPR2 antibody detects phosphorylation in response to high-efficacy agonists. T335 phosphorylation is a key regulator of FPR2 desensitization, β-arrestin...
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Agonist-induced Threonine346 phosphorylation of FPR2 Receptor
pT346-FPR2 (phospho-Formylpeptide Receptor 2...
Threonine346 (T346) is a major phosphorylation site of the FPR2 receptor. The pT346-FPR2 antibody detects phosphorylation in response to high-efficacy agonists. T346 phosphorylation is a key regulator of FPR2 desensitization, β-arrestin...
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GPR18 (non-phospho), G protein-coupled Receptor 18 Antibody
GPR18 (non-phospho), G protein-coupled...
The non-phospho-GPR18 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR18. It can be used to detect total GPR18 receptors in Western blots independent of phosphorylation. The GPR18 antibody...
375.00 € *
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NEW
Immunohistochemical identification of Neurotensin Receptor 1 in Accumbens
NTS1 (GP-IHC-grade), Neurotensin Receptor 1...
The NTS1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 1. It can be used to detect total NTS1 receptors in Western blots independent of phosphorylation. The NTS1 antibody...
375.00 € *
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Validation of the Neurotensin Receptor 1 in transfected HEK293 cells
NTS1 (GP-non-phospho), Neurotensin Receptor 1...
The NTS1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 1. It can be used to detect total NTS1 receptors in Western blots independent of phosphorylation. The NTS1 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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