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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 Atypical Chemokine Receptor 3 in Heart
ACKR3 (GP-IHC-grade), Atypical Chemokine...
The ACKR3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Atypical Chemokine Receptor 3. It can be used to detect total ACKR3 receptors in Western blots independent of phosphorylation. The...
$ 400.00 *
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Validation of the β2-Adrenoceptor in transfected HEK293 cells
β2 (GP-non-phospho), β2-Adrenoceptor Antibody,...
The non-phospho- β2 antibody is directed against the third intracellular loop of human β2 . It can be used to detect total β2 receptors in Western blots independent of phosphorylation. The non-phospho- β2 antibody can also be used to...
$ 400.00 *
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Validation of the β1-Adrenoceptor in transfected HEK293 cells
β1 (GP-non-phospho), β1-Adrenoceptor Antibody,...
The non-phospho- β1 antibody is directed against the carboxyl-terminal tail of human β1 . It can be used to detect total β1 receptors in Western blots independent of phosphorylation. The non-phospho- β1 antibody can also be used to...
$ 400.00 *
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Immunohistochemical identification of ß1-Adrenoceptor in Heart
β1 (GP-IHC-grade), β1-Adrenoceptor Antibody,...
The non-phospho- β1 antibody is directed against the carboxyl-terminal tail of human β1 . It can be used to detect total β1 receptors in Western blots independent of phosphorylation. The non-phospho- β1 antibody can also be used to...
$ 400.00 *
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Validation of the P2Y Purinoceptor 12 in transfected HEK293 cells
P2Y12 (non-phospho) P2Y Purinoceptor 12 Antibody)
The non-phospho P2Y12 antibody is directed against the distal end of the carboxyl-terminal tail human P2Y12. It can be used to detect total P2Y12 receptors in Western blots independent of phosphorylation. It can also be used to isolate...
$ 400.00 *
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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...
$ 600.00 *
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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...
$ 400.00 *
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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...
$ 400.00 *
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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...
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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...
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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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Agonist-induced Serine296/Serine297 phosphorylation of the M4 Muscarinic Acetylcholine Receptor
pS296/pS297-M4 (phospho-M4 Muscarinic...
Serine296/Serine297 is a major phosphorylation site of the M4 Muscarinic Acetylcholine Receptor. The pS296/pS297-M4 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. S296/S297...
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Agonist-induced Serine363/Threonine364 phosphorylation of the Bombesin Receptor 2
pS363/pT364-BB2 (phospho-Bombesin Receptor 2...
Serine363/Threonine364 (S363/T364) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pS363/pT364-BB2 antibody detects phosphorylation in response to agonists. S363/T364 phosphorylation is likely to be involved in...
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Agonist-induced Threonine359/Serine360 phosphorylation of the Bombesin Receptor 2
pT359/pS360-BB2 (phospho-Bombesin Receptor 2...
Threonine359/Serine360 (T359/S360) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pT359/pS360-BB2 antibody detects phosphorylation in response to agonists. T359/S360 phosphorylation is likely to be involved in...
$ 400.00 *
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Agonist-induced Threonine360/Serine361 phosphorylation of the Bombesin Receptor 3
pT360/pS361-BB3 (phospho-Bombesin Receptor 3...
Threonine360/Serine361 (T360/S361) is major phosphorylation site of the Bombesin Receptor 3 (BB3). The pT360/pS361-BB3 antibody detects phosphorylation in response to agonists. T360/S361 phosphorylation is likely to be involved in...
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Agonist-induced Serine373/Serine374 phosphorylation of the Vasopressin Receptor 1B
pS373/pS374-V1B (phospho-Vasopressin Receptor...
Serine373/Serine374 (S373/S374) is major phosphorylation site of the Vasopressin Receptor 1B (V1B). The pS373/pS374-V1B antibody detects phosphorylation in response to agonists. S373/S374 phosphorylation is likely to be involved in...
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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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