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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 CC Chemokine Receptor 5 in transfected HEK293 cells
CCR5 (GP-non-phospho) Chemokine Receptor 5...
The non-phospho-CCR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR5. It can be used to detect total CCR5 receptors in Western blots independent of phosphorylation. The CCR5 antibody can...
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Validation of the CC Chemokine Receptor 5 in transfected HEK293 cells
CCR5 (non-phospho) Chemokine Receptor 5 Antibody
The non-phospho-CCR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR5. It can be used to detect total CCR5 receptors in Western blots independent of phosphorylation. The CCR5 antibody can...
£ 335.00 *
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Validation of the Cannabinoid Receptor 2 in transfected HEK293 cells
CB2 (GP-non-phospho) Cannabinoid Receptor 2...
The non-phospho-CB2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB2. It can be used to detect total CB2 receptors in Western blots independent of phosphorylation. The CB2 antibody can also...
£ 335.00 *
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Immunohistochemical identification of Serine298/Serine300 phosphorylation of M4 Receptor in striatum
pS298/pS300-M4 (IHC-grade phospho-M4 Muscarinic...
Serine298/Serine300 is a major phosphorylation site of the M4 Muscarinic Acetylcholine Receptor. The pS298/pS300-M4 antibody detects phosphorylation in response to high-efficacy agonists but not after PKC activation. S298/S300...
£ 550.00 *
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pS364/pS366/pS368-S1P4 (phospho-Sphingosine 1-Phosphate Receptor 4 Antibody)
pS364/pS366/pS368-S1P4 (phospho-Sphingosine...
Serine364/Serine366/Serine368 (S364/S366/S368) is major phosphorylation site of the Sphingosine 1-Phosphate Receptor 4 (S1P4). The pS364/pS366/pS368-S1P4 antibody detects phosphorylation in response to agonists. S364/S366/S368...
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Agonist-induced Serine330/Serine331 phosphorylation of the Sphingosine 1-Phosphate Receptor 2
pS330/pS331-S1P2 (phospho-Sphingosine...
Serine330/Serine331 (S330/S331) is major phosphorylation site of the Sphingosine 1-Phosphate Receptor 2 (S1P2). The pS330/pS331-S1P2 antibody detects phosphorylation in response to agonists. S330/S331 phosphorylation is likely to be...
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pT342/pS343/pT345-S1P2 (phospho-Sphingosine 1-Phosphate Receptor 2 Antibody)
pT342/pS343/pT345-S1P2 (phospho-Sphingosine...
Threonine342Serine343/Threonine345 (T342/S343/T345) is major phosphorylation site of the Sphingosine 1-Phosphate Receptor 2 (S1P2). The pT342/pS343/pT345-S1P2 antibody detects phosphorylation in response to agonists. T342/S343/T345...
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Immunohistochemical identification of QRFP Receptor in heart
QRFPR (IHC-grade), QRFP Receptor Antibody
The non-phospho QRFP receptor antibody is directed against the distal end of the carboxyl-terminal tail human QRFP receptor. It can be used to detect total QRFP receptors in Western blots independent of phosphorylation. It can also be...
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Immunohistochemical identification of TP Tromboxane Receptor in pancreas
TP (IHC-grade), TP Thromboxane Receptor Antibody
The non-phospho-TP Receptor Antibody is directed against the distal end of the carboxyl-terminal tail of human TP. It can be used to detect total TP receptors in Western blots independent of phosphorylation. The non-phospho-TP antibody...
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Immunohistochemical identification of the Hydroxycarboxylic Acid Receptor 2 in spleen
HCA2 (GP-IHC-grade), Hydroxycarboxylic Acid...
The non-phospho HCA2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human HCA2 receptor. It can be used to detect total HCA2 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Immunohistochemical identification of the Hydroxycarboxylic Acid Receptor 2 in liver
HCA2 (IHC-grade), Hydroxycarboxylic Acid...
The non-phospho HCA2 receptor antibody is directed against the distal end of the carboxyl-terminal tail human HCA2 receptor. It can be used to detect total HCA2 receptors in Western blots independent of phosphorylation. It can also be...
£ 335.00 *
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Immunohistochemical identification of the Cannabinoid Receptor 2 in kidney
CB2 (IHC-grade) Cannabinoid Receptor 2 Antibody
The non-phospho-CB2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB2. It can be used to detect total CB2 receptors in Western blots independent of phosphorylation. The CB2 antibody can also...
£ 335.00 *
Details
NEW
Immunohistochemical identification of the Cannabinoid Receptor 2 in duodenum
CB2 (GP-IHC-grade) Cannabinoid Receptor 2...
The non-phospho-CB2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB2. It can be used to detect total CB2 receptors in Western blots independent of phosphorylation. The CB2 antibody can also...
£ 335.00 *
Details
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Agonist-induced Serine473/Serine475 phosphorylation of the β1-Adrenoceptor
pS473/pS475-β1 (phospho-β1-Adrenoceptor Antibody)
Serine473/Serine475 (S473/S475) is a major phosphorylation site of the β1 adrenoceptor. The pS473/pS475-β1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S473/S475...
£ 335.00 *
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Isolation and enrichment of the Smoothened Receptor from tissue lysates
SMO (GP-non-phospho) Smoothened Receptor...
The non-phospho SMO receptor antibody is directed against the distal end of the carboxyl-terminal tail human SMO receptor. It can be used to detect total SMO receptors in Western blots independent of phosphorylation. It can also be used...
£ 335.00 *
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Immunohistochemical identification of Smoothened Receptor in heart
SMO (GP-IHC-grade), Smoothened Receptor...
The non-phospho SMO receptor antibody is directed against the distal end of the carboxyl-terminal tail human SMO receptor. It can be used to detect total SMO receptors in Western blots independent of phosphorylation. It can also be used...
£ 335.00 *
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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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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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