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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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GLP2 (non-phospho) Glucagon-Like Peptide 2 Receptor Antibody
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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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...
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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...
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CB2 (GP-IHC-grade) Cannabinoid Receptor 2 Antibody, Guinea Pig
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...
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CB2 (GP-non-phospho) Cannabinoid Receptor 2 Antibody, Guinea Pig
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...
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Validation of the Cannabinoid Receptor 2 in transfected HEK293 cells
CB2 (non-phospho) 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...
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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...
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Agonist-induced Serine326 phosphorylation of the Cannabinoid Receptor 2
pS326-CB2 (phospho-Cannabinoid Receptor 2...
Serine326 (S326) is major phosphorylation site of the Cannabinoid Receptor 2 (CB2). The pS326-CB2 antibody detects phosphorylation in response to agonists. S326 phosphorylation is likely to be involved in efficient ligand sequestration...
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Agonist-induced Threonine338/Threonine340 phosphorylation of the Cannabinoid Receptor 2
pT338/pT340-CB2 (phospho-Cannabinoid Receptor 2...
Threonine338/Threonine340 (T338/T340) is major phosphorylation site of the Cannabinoid Receptor 2 (CB2). The pT338/pT340-CB2 antibody detects phosphorylation in response to agonists. T338/T340 phosphorylation is likely to be involved in...
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Agonist-induced Serine425 phosphorylation of the Cannabinoid Receptor 1
pS425-CB1 (phospho-Cannabinoid Receptor 1...
Serine425 (S425) is major phosphorylation site of the Cannabinoid Receptor 1 (CB1). The pS425-CB1 antibody detects phosphorylation in response to agonists. S425 phosphorylation is likely to be involved in efficient ligand sequestration...
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Agonist-induced Serine429 phosphorylation of the Cannabinoid Receptor 1
pS429-CB1 (phospho-Cannabinoid Receptor 1...
Serine429 (S429) is major phosphorylation site of the Cannabinoid Receptor 1 (CB1). The pS429-CB1 antibody detects phosphorylation in response to agonists. S429 phosphorylation is likely to be involved in efficient ligand sequestration...
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Agonist-induced Serine441 phosphorylation of the Cannabinoid Receptor 1
pS441-CB1 (phospho-Cannabinoid Receptor 1...
Serine441 (S441) is major phosphorylation site of the Cannabinoid Receptor 1 (CB1). The pS441-CB1 antibody detects phosphorylation in response to agonists. S441 phosphorylation is likely to be involved in efficient ligand sequestration...
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pS335/pS336-CB2 (phospho-Cannabinoid Receptor 2 Antibody)
pS335/pS336-CB2 (phospho-Cannabinoid Receptor 2...
Serine335/Serine336 (S335/S336) is major phosphorylation site of the Cannabinoid Receptor 2 (CB2). The pS335/pS336-CB2 antibody detects phosphorylation in response to agonists. S335/S336 phosphorylation is likely to be involved in...
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CB1 (IHC-grade), Cannabinoid Receptor 1 Antibody
CB1 (IHC-grade), Cannabinoid Receptor 1 Antibody
The non-phospho-CB1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB1. It can be used to detect total CB1 receptors in Western blots independent of phosphorylation. The CB1 antibody can also...
375.00 € *
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Validation of the Cannabinoid Receptor 1 in transfected HEK293 cells
CB1 (non-phospho) Cannabinoid Receptor 1 Antibody
The non-phospho-CB1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB1. It can be used to detect total CB1 receptors in Western blots independent of phosphorylation. The CB1 antibody can also...
375.00 € *
Details
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CB1 (GP-non-phospho) Cannabinoid Receptor 1 Antibody, Guinea Pig
CB1 (GP-non-phospho) Cannabinoid Receptor 1...
The non-phospho-CB1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CB1. It can be used to detect total CB1 receptors in Western blots independent of phosphorylation. The CB1 antibody can also...
375.00 € *
Details
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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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