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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 APLN Receptor in human pancreas
APLNR (IHC-grade), Apelin Receptor Antibody
The non-phospho-APLNR antibody is directed against the distal end of the carboxyl-terminal tail of human apelin receptor. It also detects APLNR in cultured cells and tissue sections by immunohistochemistry. It can be used to detect total...
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Detection of non-phosphorylated human FFA4 Receptor
FFA4 (non-phospho-FFA4 Antibody)
The non-phospho-FFA4 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human FFA4. It can be used to detect total FFA4 receptors in Western blots independent of phosphorylation. The non-phospho-FFA4...
$ 375.00 *
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Validation of the GPR15 Receptor in transfected HEK293 cells
GPR15 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR15 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR15. It can be used to detect total GPR15 receptors in Western blots independent of phosphorylation. The GPR15 antibody...
$ 375.00 *
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Validation of the GPR26 Receptor in transfected HEK293 cells
GPR26 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR26 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR26. It can be used to detect total GPR26 receptors in Western blots independent of phosphorylation. The GPR26 antibody...
$ 375.00 *
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Validation of the GPR34 Receptor in transfected HEK293 cells
GPR34 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR34 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR34. It can be used to detect total GPR34 receptors in Western blots independent of phosphorylation. The GPR34 antibody...
$ 375.00 *
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Validation of the SUCNR1 Receptor in transfected HEK293 cells
SUCNR1/GPR91 (non-phospho), Succinate Receptor...
The non-phospho-SUCNR1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SUCNR1. It can be used to detect total SUCNR1 receptors in Western blots independent of phosphorylation. The SUCNR1...
$ 375.00 *
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Validation of the GPR39 Receptor in transfected HEK293 cells
GPR39 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR39 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR39. It can be used to detect total GPR39 receptors in Western blots independent of phosphorylation. The GPR39 antibody...
$ 375.00 *
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Validation of the GPR97/ADGR3G Receptor in transfected HEK293 cells
GPR97/ADGRG3 (non-phospho), G protein-coupled...
The non-phospho-GPR97/ADGRG3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR97/ADGRG3. It can be used to detect total GPR97/ADGRG3 receptors in Western blots independent of phosphorylation....
$ 375.00 *
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Validation of the GPR101 Receptor in transfected HEK293 cells
GPR101 (non-phospho), G protein-coupled...
The non-phospho-GPR101 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR101. It can be used to detect total GPR101 receptors in Western blots independent of phosphorylation. The GPR101...
$ 375.00 *
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Validation of the GPR31 Receptor in transfected HEK293 cells
GPR31 (non-phospho), G protein-coupled...
The non-phospho-GPR31 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR31. It can be used to detect total GPR3 receptors in Western blots independent of phosphorylation. The GPR31 antibody...
$ 375.00 *
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Validation of the M5 Muscarinic Acetylcholine Receptor in transfected HEK293 cells
M5 (non-phospho-M5 Muscarinic Acetylcholine...
The non-phospho-M5 receptor antibody is directed against the 3rd loop of human M5 Muscarinic Acetylcholine Receptor (M5). It can be used to detect total M5 receptors in Western blots independent of phosphorylation. The non-phospho-M5...
$ 375.00 *
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Validation of the M1 Muscarinic Acetylcholine Receptor in transfected HEK293 cells
M1 (non-phospho-M1 Muscarinic Acetylcholine...
The non-phospho-M1 receptor antibody is directed against the 3rd loop of human M1 Muscarinic Acetylcholine Receptor (M1). It can be used to detect total M1 receptors in Western blots independent of phosphorylation. The non-phospho-M1...
$ 375.00 *
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Validation of the M4 Muscarinic Acetylcholine Receptor in transfected HEK293 cells
M4 (non-phospho-M4 Muscarinic Acetylcholine...
The non-phospho-M4 receptor antibody is directed against the 3rd loop of human M4 Muscarinic Acetylcholine Receptor (M4). It can be used to detect total M4 receptors in Western blots independent of phosphorylation. The non-phospho-M4...
$ 375.00 *
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Validation of the GPR52 Receptor in transfected HEK293 cells
GPR52 (non-phospho), G protein-coupled...
The non-phospho-GPR52 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR52. It can be used to detect total GPR52 receptors in Western blots independent of phosphorylation. The GPR52 antibody...
$ 375.00 *
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Validation of the GPR139 Receptor in transfected HEK293 cells.
GPR139 (non-phospho), G protein-coupled...
The non-phospho-GPR139 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR139. It can be used to detect total GPR139 receptors in Western blots independent of phosphorylation. The GPR139...
$ 375.00 *
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Validation of the GPR88 Receptor in transfected HEK293 cells
GPR88 (non-phospho), G protein-coupled...
The non-phospho-GPR88 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR88. It can be used to detect total GPR3 receptors in Western blots independent of phosphorylation. The GPR88 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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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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