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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 the Glucagon Receptor in pancreas
GCGR (IHC-grade), Glucagon Receptor Antibody
The GCGR antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GCGR. It can be used to detect total GCGR receptors in Western blots independent of phosphorylation. The GCGR antibody can also be...
$ 400.00 *
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Agonist-induced Threonine332/Serine335 phosphorylation of the Lysophosphatidic Acid Receptor 6
pT332/pS335-LPA6 (phospho-Lysophosphatidic Acid...
Threonine332/Serine335 (T332/S335) is major phosphorylation site of the Lysophosphatidic Acid Receptor 6 (LPA6). pT332/pS335-LPA6 antibody detects phosphorylation in response to agonists. T332/S335 phosphorylation is likely to be...
$ 400.00 *
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Agonist-induced Serine357 phosphorylation of the Chemokine Receptor 6
pS357-CCR6 (phospho-Chemokine Receptor 6 Antibody)
Serine357 (S357) is a major phosphorylation site of the CCR6 receptor. The pS357-CCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S357 phosphorylation is a key regulator of...
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Agonist-induced Threonine360/Serine361 phosphorylation of the Chemokine Receptor 6
pT360/pS361-CCR6 (phospho-Chemokine Receptor 6...
Threonine360/Serine361 (T360/S361) is a major phosphorylation site of the CCR6 receptor. The pT360/pS361-CCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. T360/S361...
$ 400.00 *
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Agonist-induced Threonine363 phosphorylation of the Chemokine Receptor 6
pT363-CCR6 (phospho-Chemokine Receptor 6 Antibody)
Threonine363 (T363) is a major phosphorylation site of the CCR6 receptor. The pT363-CCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. T363 phosphorylation is a key regulator of...
$ 400.00 *
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Immunohistochemical identification of SUCNR1 Receptor in Pancreas
SUCNR1/GPR91 (IHC-grade), Succinate Receptor...
The 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 antibody can also...
$ 400.00 *
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Immunohistochemical identification of GPR6 Receptor in small intestine
GPR6 (IHC-grade), G Protein-Coupled Receptor 6...
The GPR6 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP6. It can be used to detect total GPR6 receptors in Western blots independent of phosphorylation. The GPR6 antibody can also be...
$ 400.00 *
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Agonist-induced Serine501/Threonine503/Serine504 phosphorylation of the Parathyroid Hormone Receptor 1
pS501/pT503/pS504-PTH1 (phospho-Parathyroid...
Serine501/Threonine503/Serine504 (S501/T503/S504) is major phosphorylation site of the Parathyroid Hormone Receptor 1 (PTH1). The pS501pT503/pS504-PTH1 antibody detects phosphorylation in response to agonists. S501T503/S504...
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Agonist-induced Serine492/Serine493 phosphorylation of the Parathyroid Hormone Receptor 1
pS492/pS493-PTH1 (phospho-Parathyroid Hormone...
Serine492/Serine493 (S492/S493) is major phosphorylation site of the Parathyroid Hormone Receptor 1 (PTH1). The pS492/pS493-PTH1 antibody detects phosphorylation in response to agonists. S492/S493 phosphorylation is likely to be involved...
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Agonist-induced Serine354/Threonine357/Threonine358 phosphorylation of the Lysophosphatidic Acid Receptor 4
pS354/pT357/pT358-LPA4...
Serine354/Threonine357/Threonine358 (S354/T357/T358) is major phosphorylation site of the Lysophosphatidic Acid Receptor 4 (LPA4). The pS354/pT357/pT358-LPA4 antibody detects phosphorylation in response to agonists. S354/T357/T358...
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Agonist-induced Threonine341/Threonine342/Serine345 phosphorylation of the Lysophosphatidic Acid Receptor 4
pT341/pT342/pS345-LPA4...
Threonine341/Threonine342/Serine345 (T341/T342/S345) is major phosphorylation site of the Lysophosphatidic Acid Receptor 4 (LPA4). The pT341/pT342/pS345-LPA4 antibody detects phosphorylation in response to agonists. T341/T342/S345...
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Agonist-induced Threonine336/Threonine338 phosphorylation of the Lysophosphatidic Acid Receptor 4
pT336/pT338-LPA4 (phospho-Lysophosphatidic Acid...
Threonine336/Threonine338 (T336/T338) is major phosphorylation site of the Lysophosphatidic Acid Receptor 4 (LPA4). The pT336/pT338-LPA4 antibody detects phosphorylation in response to agonists. T336/T338 phosphorylation is likely to be...
$ 400.00 *
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Agonist-induced Threonine351 phosphorylation of the Lysophosphatidic Acid Receptor 1
pT351-LPA1 (phospho-Lysophosphatidic Acid...
Threonine351 (T351) is major phosphorylation site of the Lysophosphatidic Acid Receptor 1 (LPA1). The pT351-LPA1 antibody detects phosphorylation in response to agonists. T351 phosphorylation is likely to be involved in efficient ligand...
$ 400.00 *
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Agonist-induced Serine344/Serine346/Serine347 phosphorylation of the Lysophosphatidic Acid Receptor 1
pS344/pS346/pS347-LPA1...
Serine344/Serine346/Serine347 (S344/S346/S347) is major phosphorylation site of the Lysophosphatidic Acid Receptor 1 (LPA1). The pS344/pS346/pS347-LPA1 antibody detects phosphorylation in response to agonists. S344/S346/S347...
$ 400.00 *
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Agonist-induced Threonine338/Serine341 phosphorylation of the Lysophosphatidic Acid Receptor 1
pT338/pS341-LPA1 (phospho-Lysophosphatidic Acid...
Threonine338/Serine341 (T338/S341) is major phosphorylation site of the Lysophosphatidic Acid Receptor 1 (LPA1). The pT338/pS341-LPA1 antibody detects phosphorylation in response to agonists. T338/S341 phosphorylation is likely to be...
$ 400.00 *
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Validation of the δ-Opioid Receptor in transfected HEK293 cells
DOP (GP-non-phospho) δ-Opioid Receptor...
The non-phospho-δ-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.
$ 400.00 *
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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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