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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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NEW
Validation of the GPR85 Receptor in transfected HEK293 cells.
GPR85 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR85 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR85. It can be used to detect total GPR85 receptors in Western blots independent of phosphorylation. The GPR85 antibody...
$ 375.00 *
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NEW
GPR85 (IHC-Grade), G protein-coupled Receptor 85 Antibody
GPR85 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR85 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR85. It can be used to detect total GPR85 receptors in Western blots independent of phosphorylation. The GPR85 antibody...
$ 375.00 *
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NEW
Serine422/Serine423 phosphorylation of the G-protein coupled Receptor 75
pS422/pS423-GPR75 (phospho-GPR75 Antibody)
Serine422/Serine423 (S422/S423) is a major phosphorylation site of the human GPR75 receptor. The pS422/pS423-GPR75 antibody detects GRK-mediated constitutive phosphorylation as well as PKC-mediated phosphorylation of GPR75 when expressed...
$ 375.00 *
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Threonine427/Serine429 phosphorylation of the G-protein coupled Receptor 75.
pT427/pS429-GPR75 (phospho-GPR75 Antibody)
Threonine427/Serine429 (T427/S429) is a major phosphorylation site of the human GPR75 receptor. The pT427/pS429-GPR75 antibody detects GRK-mediated constitutive phosphorylation of GPR75 when expressed in HEK293 cells.
$ 375.00 *
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NEW
Immunohistochemical identification of Threonine 427/Serine429 phosphorylation of G-protein coupled Receptor 75 in mouse brain
pT427/pS429-GPR75 (IHC-grade phospho-GPR75...
Threonine427/Serine429 (T427/S429) is a major phosphorylation site of the human GPR75 receptor. The pT427/pS429-GPR75 antibody detects GRK-mediated constitutive phosphorylation of GPR75 when expressed in HEK293 cells.
$ 500.00 *
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NEW
Validation of the GPR75 Receptor in transfected HEK293 cells.
GPR75 (non-phospho), G protein-coupled...
The non-phospho-GPR75 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR75. It can be used to detect total GPR75 receptors in Western blots independent of phosphorylation. The GPR75 antibody...
$ 375.00 *
Details
NEW
Validation of the GPR75 Receptor in transfected HEK293 cells
GPR75 (GP-non-phospho), G protein-coupled...
The non-phospho-GPR75 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR75. It can be used to detect total GPR75 receptors in Western blots independent of phosphorylation. The GPR75 antibody...
$ 375.00 *
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NEW
GPR75 (GP-IHC-Grade), G protein-coupled Receptor 75 Antibody, Guinea Pig
GPR75 (GP-IHC-Grade), G protein-coupled...
The non-phospho-GPR75 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR75. It can be used to detect total GPR75 receptors in Western blots independent of phosphorylation. The GPR75 antibody...
$ 375.00 *
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NEW
Validation of the GPR37L1 Receptor in transfected HEK293 cells
GPR37L1 (non-phospho), G protein-coupled...
The non-phospho-GPR37L1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR37L1. It can be used to detect total GPR37L1 receptors in Western blots independent of phosphorylation. The GPR37L1...
$ 375.00 *
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GPR37L1 (IHC-Grade), G protein-coupled Receptor 37L1 Antibody
GPR37L1 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR37L1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR37L1. It can be used to detect total GPR37L1 receptors in Western blots independent of phosphorylation. The GPR37L1...
$ 375.00 *
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NEW
Validation of the GPR68 Receptor in transfected HEK293 cells.
GPR68 (non-phospho), G protein-coupled Receptor...
The non-phospho-GPR68 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR68. It can be used to detect total GPR68 receptors in Western blots independent of phosphorylation. The GPR68 antibody...
$ 375.00 *
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NEW
GPR68 (IHC-Grade), G protein-coupled Receptor 68 Antibody
GPR68 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR68 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR68. It can be used to detect total GPR68 receptors in Western blots independent of phosphorylation. The GPR68 antibody...
$ 375.00 *
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Validation of the GPBA Receptor in transfected HEK293 cells.
GPBA (non-phospho), Bile Acid Receptor Antibody
The non-phospho-GPBA receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPBA. It can be used to detect total GPBA receptors in Western blots independent of phosphorylation. The GPBA antibody can...
$ 375.00 *
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GPBA (IHC-Grade), Bile Acid Receptor Antibody
GPBA (IHC-Grade), Bile Acid Receptor Antibody
The non-phospho-GPBA receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPBA. It can be used to detect total GPBA receptors in Western blots independent of phosphorylation. The GPBA antibody can...
$ 375.00 *
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Rabbit Monoclonal
KD-Validated
NEW
SST3 [UMB5] (RM-IHC-grade), Somatostatin Receptor 3 Antibody, Rabbit Monoclonal
SST3 [UMB5] (RM-IHC-grade), Somatostatin...
The SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Somatostatin Receptor 3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The SST3...
$ 495.00 *
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Rabbit Monoclonal
NEW
V1A [UMB21] (RM-IHC-Grade-Vasopressin Receptor 1A Antibody), Rabbit Monoclonal
V1A [UMB21] (RM-IHC-Grade-Vasopressin Receptor...
The non-phospho-V1A antibody is directed against the distal end of the carboxyl-terminal tail of human V1A. It can be used to detect total V1A receptors in Western blots independent of phosphorylation. The V1A antibody can also be used...
$ 495.00 *
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23 From 43

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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