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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 CCR8 Receptor in transfected HEK293 cells
CCR8 (non-phospho), CCR8 Chemokine Receptor...
The non-phospho-CCR8 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR8. It can be used to detect total CCR8 receptors in Western blots independent of phosphorylation. The non-phospho-CCR8...
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Validation of the Angiotensin Receptor 2 in transfected HEK293 cells
AT2 (non-phospho-Angiotensin Receptor 2 Antibody)
The non-phospho-AT2 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human Angiotensin Receptor 2 (AT2). It can be used to detect total AT2 receptors in Western blots independent of phosphorylation....
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Indentification of GPR183 Receptor in mouse tissues
GPR183 (GP-non-phospho), Oxysterol Receptor...
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...
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Validation of the Lysophosphatidic Acid Receptor 6 in transfected HEK293 cells.
LPA6 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA6 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA6. It can be used to detect total LPA6 receptors in Western blots independent of phosphorylation. The LPA6 antibody can...
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Indentification of SUCNR1 Receptor in mouse tissues
SUCNR1/GPR91 (GP-non-phospho), Succinate...
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...
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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...
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Immunohistochemical identification of M1 Muscarinic Acetylcholine Receptor in hippocampus
M1 (IHC-grade), 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...
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Immunohistochemical identification of Serine351/Threonine356 phosphorylation of G-protein coupled Receptor 17 in oligodendrocytes
pS351/pT356-GPR17 (IHC-Grade phospho-GPR17...
Serine351/Threonine356 (S351/T356) is a major phosphorylation site of the human GPR17 receptor. The pS351/pT356-GPR17 antibody detects phosphorylation in response to high-efficacy agonists. S351/T356 phosphorylation is a key regulator of...
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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...
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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...
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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...
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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...
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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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Immunohistochemical identification of GPR183 Receptor in human spleen
GPR183 (IHC-grade), 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...
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Validation of the APLN Receptor in transfected HEK293 cells
APLNR (non-phospho), 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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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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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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