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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 GPR22 Receptor in Pancreas
GPR22 (IHC-grade), G Protein-Coupled Receptor...
The GPR22 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP22. It can be used to detect total GPR22 receptors in Western blots independent of phosphorylation. The GPR22 antibody can...
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NEW
Agonist-induced Serine412 phosphorylation of the β1-Adrenoceptor
pS412-β1 (phospho-β1-Adrenoceptor Antibody)
Serine412 (S412) is a major phosphorylation site of the β1 adrenoceptor. The pS412-β1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S412 phosphorylation is primarily...
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Agonist-induced Threoine347/Serine349 phosphorylation of GPR183
pT347/pT349-GPR183 (phospho-GPR183 Antibody)
Threonine347/Threonine349 (T347/T349) is major phosphorylation site of human GPR183 receptor. The pT347/pT349-GPR183 antibody detects phosphorylation in response to agonists. T347/T349 phosphorylation is likely to be involved in...
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Agonist-induced Serine346/Serine347 phosphorylation of the Angiotensin Receptor 1
pS346/pS347-AT1 (phospho-Angiotensin Receptor 1...
Serine346/Serine347 (S346/S347) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS346/pS347-AT1 antibody detects phosphorylation in response to agonists. S346/S347 phosphorylation is likely to be involved in...
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Agonist-induced Serine335/Threonine336 phosphorylation of the Angiotensin Receptor 1
pS335/pT336-AT1 (phospho-Angiotensin Receptor 1...
Serine335/Threonine336 (S335/T336) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS335/pT336-AT1 antibody detects phosphorylation in response to agonists. S335/T336 phosphorylation is likely to be involved in...
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KO-Validated
Western blot analysis of G Protein-coupled Receptor 20 in mouse tissues in vivo.
mGPR20 (non-phospho-G Protein-Coupled Receptor...
The GPR20 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse GPR20. It can be used to detect total GPR20 receptors in Western blots independent of phosphorylation. The GPR20 antibody can also be...
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KO-Validated
Immunohistochemical identification of G Protein-coupled Receptor 20 in mouse spleen.
mGPR20 (IHC-grade), G Protein-Coupled Receptor...
The GPR20 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse GPR20. It can be used to detect total GPR20 receptors in Western blots independent of phosphorylation. The GPR20 antibody can also be...
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Agonist-induced Serine401 phosphorylation of the Neurotensin Receptor
pS401-NTS1 (phospho-Neurotensin Receptor 1...
Serine401 (S401) is major phosphorylation site of the Neurotensin Receptor 1 (NTS1). The pS401-NTS1 antibody detects phosphorylation in response to agonists. S401 phosphorylation is likely to be involved in efficient ligand sequestration...
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Agonist-induced Serine403/Serine404 phosphorylation of the Neurotensin Receptor 1
pS403/pS404-NTS1 (phospho-Neurotensin Receptor...
Serine403/Serine404 (S403/S404) is major phosphorylation site of the Neurotensin Receptor 1 (NTS1). The pS403/pS404-NTS1 antibody detects phosphorylation in response to agonists. S403/S404 phosphorylation is likely to be involved in...
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Agonist-induced Serine409/Serine410 phosphorylation of the Neurotensin Receptor 1
pS409/pS410-NTS1 (phospho-Neurotensin Receptor...
Serine409/Serine410 (S409/S410) is major phosphorylation site of the Neurotensin Receptor 1 (NTS1). The pS409/pS410-NTS1 antibody detects phosphorylation in response to agonists. S409/S410 phosphorylation is likely to be involved in...
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Immunohistochemical identification of Serine409/Serine410 phosphorylation of Neurotensin Receptor 1 in mouse brain.
pS409/pS410-NTS1 (IHC-grade phospho-Neurotensin...
Serine409/Serine410 (S409/S410) is major phosphorylation site of the Neurotensin Receptor 1 (NTS1). The pS409/pS410-NTS1 antibody detects phosphorylation in response to agonists. S409/S410 phosphorylation is likely to be involved in...
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Immunohistochemical identification of G Protein-coupled Receptor 87 in kidney.
GPR87 (IHC-grade), G Protein-Coupled Receptor...
The GPR87 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP87. It can be used to detect total GPR87 receptors in Western blots independent of phosphorylation. The GPR87 antibody can...
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Constitutive Serine296/Serine297 phosphorylation of the FFA Receptor 2
pS296/pS297-FFA2 (phospho-FFA2 Antibody)
Serine296/Serine297 (S296/S297) is major phosphorylation site of the FFA Receptor 2 (FFA2). The pS296/pS297-FFA2 antibody detects constitutive phosphorylation of FFA2.
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Validation of the δ-Opioid Receptor in transfected HEK293 cells
DOP (non-phospho) δ-Opioid Receptor Antibody
The non-phospho-∂-opioid receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human DOP. It can be used to detect total DOP receptors in Western blots independent of phosphorylation.
375.00 € *
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Citations
Agonist-induced Serine363 phosphorylation of the δ-Opioid receptor.
pS363-DOP (phospho-δ-Opioid Receptor Antibody)
Serine363 (S363) is the primary phosphorylation site in a hierarchical phosphorylation cascade of the delta-opioid receptor (DOP). The pS363-DOP antibody detects phosphorylation in response to high- and low-efficacy agonists but not...
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Citations
Agonist-induced Threonine361 phosphorylation of the δ-Opioid Receptor.
pT361-DOP (phospho-δ-Opioid Receptor Antibody)
Threonine361 (T361) is a major phosphorylation site of the delta-opioid receptor (DOP). The pT361-DOP antibody detects phosphorylation in response to agonists but not after PKC activation. T361 phosphorylation is a key regulator of DOP...
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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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