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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 GPR183 Receptor in transfected HEK293 cells
GPR183 (non-phospho), Oxysterol Receptor Antibody
The non-phospho-GPR183 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR183. It also detects GPR183 in cultured cells and tissue sections by immunohistochemistry. It can be used to detect...
$ 375.00 *
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NEW
Validation of the G protein-coupled receptor 32 in transfected HEK293 cells
GPR32 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR32 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR32. It can be used to detect total GPR32 receptors in Western blots independent of phosphorylation. The GPR32 antibody...
$ 375.00 *
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NEW
Validation of the GPR27 Receptor in transfected HEK293 cells
GPR27 (non-phospho), G protein-coupled...
The non-phospho-GPR27 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR27. It can be used to detect total GPR27 receptors in Western blots independent of phosphorylation. The GPR27 antibody...
$ 375.00 *
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NEW
Validation of the GPR12 Receptor in transfected HEK293 cells
GPR12 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR12 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR12. It can be used to detect total GPR12 receptors in Western blots independent of phosphorylation. The GPR12 antibody...
$ 375.00 *
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NEW
Validation of the GPR6 Receptor in transfected HEK293 cells.
GPR6 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR6 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR6. It can be used to detect total GPR6 receptors in Western blots independent of phosphorylation. The GPR6 antibody can...
$ 375.00 *
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NEW
Validation of the MRGPRX2 Receptor in transfected HEK293 cells
MRGPRX2 (GP-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...
$ 375.00 *
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NEW
Immunohistochemical identification of MRGPRX2 Receptor in Pancreas
MRGPRX2 (GP-IHC-grade), 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...
$ 375.00 *
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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...
$ 375.00 *
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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...
$ 375.00 *
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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...
$ 375.00 *
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NEW
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...
$ 375.00 *
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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...
$ 375.00 *
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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...
$ 375.00 *
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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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NEW
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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NEW
CX3CR1 (non-phospho), CX3C Chemokine Receptor 1 Antibody
CX3CR1 (non-phospho), CX3C Chemokine Receptor 1...
The non-phospho-CX3CR1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human CX3CR1. It can be used to detect total CX3CR1 receptors in Western blots independent of phosphorylation.
$ 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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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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