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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 Glucagon-Like Peptide 2 Receptor in transfected HEK293 cells
GLP2 (non-phospho) Glucagon-Like Peptide 2...
The non-phospho GLP2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human GLP2 receptor. It can be used to detect total GLP2 receptors in Western blots independent of phosphorylation. It can also be...
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Immunohistochemical identification of Glucagon-Like Peptide 2 Receptor in enteric ganglion
GLP2 (IHC-grade), Glucagon-Like Peptide 2...
The non-phospho GLP2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human GLP2 receptor. It can be used to detect total GLP2 receptors in Western blots independent of phosphorylation. It can also be...
$ 375.00 *
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Validation of the Glucagon Receptor in transfected HEK293 cells
GCGR (non-phospho) Glucagon Receptor Antibody
The non-phospho GCGR antibody is directed against the distal end of the carboxyl-terminal tail of human GCGR. It can be used to detect total GCGR receptors in Western blots independent of phosphorylation. It can also be used to isolate...
$ 375.00 *
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Validation of the Gastric Inhibitory Polypeptide Receptor in transfected HEK293 cells
GIPR (non-phospho) Gastric Inhibitory...
The non-phospho GIPR antibody is directed against the distal end of the carboxyl-terminal tail human GIPR. It can be used to detect total GIPR receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
$ 375.00 *
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Immunohistochemical Identification of Threonine306/Threonine310 phosphorylation of the FFA Receptor 2 in mouse neuroendocrine cells and peyer's patches.
pT306/pT310-FFA2 (IHC-grade phospho-FFA2 Antibody)
Threonine306/Threonine310 (T306/T310) is major phosphorylation site of the FFA 2 Receptor (FFA2). The pT306/pT310-FFA2 antibody detects phosphorylation in response to agonists. T306/T310 phosphorylation is likely to be involved in...
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Immunohistochemical Identification of Serine594/Threonine597/Serine599 phosphorylation of the SMO Receptor in primary cilia in the mouse neural tube
pS594/pT597/pS599-SMO (IHC-grade phospho-SMO...
Serine594/Threonine597/Serine599 (S594/T597/S599) is major GRK2 phosphorylation site of the SMO receptor. The pS594/pT597/pS599-SMO antibody detects phosphorylation in response to agonists. The pS594/pT597/pS599-SMO antibody can be used...
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Agonist-induced Serine422/Serine425 phosphorylation of the Calcitonin Recepto
pS422/pS425-CT (phospho-Calcitonin Receptor...
Serine422/Serine425 (S422/S425) is a major phosphorylation site of the Calcitonin receptor. The pS422/pS425-CT antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S422/S425...
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Agonist-induced Threonine311/Serine312 phosphorylation of the A3 Adenosine Receptor.
pT311/pS312-A3 (phospho-A3 Adenosine Receptor...
Threonine311/Serine312 is a major phosphorylation site of the A3 Adenosine receptor. The pT311/pS312-A3 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. T311/S312 phosphorylation is a...
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Agonist-induced Serine338/Threonine342/Threonine345 phosphorylation of the M5 Muscarinic Acetylcholine Receptor
pS338/pT342/pT345-M5 (phospho-M5 Muscarinic...
Serine338/Threonine342/Threonine345 is a major phosphorylation site of the M5 Muscarinic Acetylcholine Receptor. The pS338/pT342/pT345-M5 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC...
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Agonist-induced Threonine306/Threonine310 phosphorylation of the FFA2 Receptor
pT306/pT310-FFA2 (phospho-FFA2 Antibody)
Threonine306/Threonine310 (T306/T310) is major phosphorylation site of the FFA 2 Receptor (FFA2). The pT306/pT310-FFA2 antibody detects phosphorylation in response to agonists. T306/T310 phosphorylation is likely to be involved in...
$ 375.00 *
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Agonist-induced Threonine347 phosphorylation of the FFA Receptor 4
pT347-FFA4 (phospho-FFA4 Antibody)
Threonine347 (T347) is major phosphorylation site of the FFA Receptor 4 (FFA4). The pT347-FFA4 antibody detects phosphorylation in response to agonists. T347 phosphorylation is likely to be involved in efficient ligand sequestration by...
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Agonist-induced Serine305/Serine306 phosphorylation of the FFA Receptor 3
pS305/pS306-FFA3 (phospho-FFA3 Antibody)
Serine305/Serine306 (S305/S306) is major phosphorylation site of the FFA Receptor 3 (FFA3). The pS305/pS306-FFA3 antibody detects phosphorylation in response to agonists. S305/S306 phosphorylation is likely to be involved in efficient...
$ 375.00 *
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Agonist-induced Threonine328/Serine329 phosphorylation of the FFA Receptor 3
pT328/pS329-FFA3 (phospho-FFA3 Antibody)
Threonine328/Serine329 (T328/S329) is major phosphorylation site of the FFA Receptor 3 (FFA3). The pT328/pS329-FFA3 antibody detects phosphorylation in response to agonists. T328/S329 phosphorylation is likely to be involved in efficient...
$ 375.00 *
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Agonist-induced Serine329 phosphorylation of the A2A Adenosine Receptor
pS329-A2A (phospho-A2A Adenosine Receptor...
Serine329 is a major phosphorylation site of the A2A Adenosine receptor. The pS329-A2A antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. S329 phosphorylation is a key regulator of A2A...
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Validation of the A2A Adenosine Receptor in transfected HEK293 cells
A2A (non-phospho) Adenosine 2A Receptor Antibody
The non-phospho-A2A receptor antibody is directed against the distal end of the carboxyl-terminal tail of human A2A. It can be used to detect total A2A receptors in Western blots independent of phosphorylation. The A2A antibody can also...
$ 375.00 *
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Validation of the A2A Adenosine Receptor in transfected HEK293 cells
A2A (GP-non-phospho) Adenosine 2A Receptor...
The non-phospho-A2A receptor antibody is directed against the distal end of the carboxyl-terminal tail of human A2A. It can be used to detect total A2A receptors in Western blots independent of phosphorylation. The A2A antibody can also...
$ 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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