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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 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 human GCGR. It can be used to detect total GCGR receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
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NEW
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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NEW
Agonist-induced Serine348/Threonine349 phosphorylation of the Angiotensin Receptor 1
pS348/pT349-AT1 (phospho-Angiotensin Receptor 1...
Serine348/Threonine349 (S348/T349) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS348/pT349-AT1 antibody detects phosphorylation in response to agonists. S348/T349 phosphorylation is likely to be involved in...
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NEW
Agonist-induced Serine338/Serine342 phosphorylation of the Angiotensin Receptor 1
pS338/pS342-AT1 (phospho-Angiotensin Receptor 1...
Serine338/Serine342 (S338/S342) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS338/pS342-AT1 antibody detects phosphorylation in response to agonists. S338/S342 phosphorylation is likely to be involved in...
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NEW
Agonist-induced Serine326/Serine328 phosphorylation of the Angiotensin Receptor 1
pS326/pS328-AT1 (phospho-Angiotensin Receptor 1...
Serine326/Serine328 (S328/S328) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS326/pS328-AT1 antibody detects phosphorylation in response to agonists. S328/S328 phosphorylation is likely to be involved in...
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NEW
Immunohistochemical identification of G Protein-coupled Receptor 17 in oligodendrocytes
GPR17 (GP-IHC-grade), G Protein-Coupled...
The GPR17 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP17. It can be used to detect total GPR17 receptors in Western blots independent of phosphorylation. The GPR17 antibody can...
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SAMPLE PACK
Agonist-induced Serine331/Threonine332 phosphorylation of the Angiotensin Receptor 1
AT1 Sample Pack (phospho- and...
AT1 Sample Pack consisting of all four available phospho- and non-phospho-AT1 Antibodies 7 x 20 µL trial size each.
300.00 € *
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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...
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Agonist-induced Threonine323/Serine324/Serine325 phosphorylation of the Lysophosphatidic Acid Receptor 2
pT323/pS324/pS325-LPA2...
Threonine323/Serine324/Serine325 (T323/S324/325) is major phosphorylation site of the Lysophosphatidic Acid Receptor 2 (LPA2). pT323/pS324/pS325-LPA2 antibody detects phosphorylation in response to agonists. T323/S324/325 phosphorylation...
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NEW
Agonist-induced Serine331/Threonine332 phosphorylation of the Lysophosphatidic Acid Receptor 2
pS331/pT332-LPA2 (phospho-Lysophosphatidic Acid...
Serine331/Threonine332 (S331/T332) is major phosphorylation site of the Lysophosphatidic Acid Receptor 2 (LPA2). pS331/pT332-LPA2 antibody detects phosphorylation in response to agonists. S331/T332 phosphorylation is likely to be...
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NEW
Immunohistochemical identification of the Formylpeptide Receptor 2 in striatum
FPR2 (IHC-grade), Formylpeptide Receptor 2...
The FPR2 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human FPR2. It can be used to detect total FPR2 receptors in Western blots independent of phosphorylation. The FPR2 antibody can also be...
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NEW
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...
375.00 € *
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NEW
Immunohistochemical identification of G Protein-coupled Receptor 82 in hippocampus
GPR82 (IHC-grade), G Protein-Coupled Receptor...
The GPR82 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP82. It can be used to detect total GPR82 receptors in Western blots independent of phosphorylation. The GPR82 antibody can...
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NEW
Immunohistochemical identification of GPR32 Receptor in Small Intestine
GPR32 (IHC-grade), G Protein-Coupled Receptor...
The GPR32 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP32. It can be used to detect total GPR32 receptors in Western blots independent of phosphorylation. The GPR32 antibody can...
375.00 € *
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NEW
Immunohistochemical identification of GPR27 Receptor in small intestine
GPR27 (IHC-grade), G Protein-Coupled Receptor...
The GPR27 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP27. It can be used to detect total GPR27 receptors in Western blots independent of phosphorylation. The GPR27 antibody can...
375.00 € *
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NEW
Immunohistochemical identification of GPR12 Receptor in kidney
GPR12 (IHC-grade), G Protein-Coupled Receptor...
The GPR12 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP12. It can be used to detect total GPR12 receptors in Western blots independent of phosphorylation. The GPR12 antibody can...
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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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