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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 G Protein-coupled Receptor 17 in oligodendrocytes.
GPR17 (IHC-grade), G Protein-Coupled Receptor...
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...
375.00 € *
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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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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...
375.00 € *
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NEW
Immunohistochemical identification of GPR6 Receptor in small intestine
GPR6 (IHC-grade), G Protein-Coupled Receptor 6...
The GPR6 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP6. It can be used to detect total GPR6 receptors in Western blots independent of phosphorylation. The GPR6 antibody can also be...
375.00 € *
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NEW
Immunohistochemical identification of GPR25 Receptor in small intestine
GPR25 (IHC-grade), G Protein-Coupled Receptor...
The GPR25 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP25. It can be used to detect total GPR25 receptors in Western blots independent of phosphorylation. The GPR25 antibody can...
375.00 € *
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NEW
Immunohistochemical identification of GPR22 Receptor in Pancreas
GPR22 (IHC-grade), G Protein-Coupled Receptor...
The GPR22 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human GRP22. It can be used to detect total GPR22 receptors in Western blots independent of phosphorylation. The GPR22 antibody can...
375.00 € *
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NEW
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...
375.00 € *
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NEW
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...
375.00 € *
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NEW
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...
375.00 € *
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Agonist-induced Serine412 phosphorylation of the β1-Adrenoceptor
pS412-β1 (phospho-β1-Adrenoceptor Antibody)
Serine412 (S412) is a major phosphorylation site of the β1 adrenoceptor. The pS412-β1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S412 phosphorylation is primarily...
375.00 € *
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Agonist-induced Threoine347/Serine349 phosphorylation of GPR183
pT347/pT349-GPR183 (phospho-GPR183 Antibody)
Threonine347/Threonine349 (T347/T349) is major phosphorylation site of human GPR183 receptor. The pT347/pT349-GPR183 antibody detects phosphorylation in response to agonists. T347/T349 phosphorylation is likely to be involved in...
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NEW
Agonist-induced Serine346/Serine347 phosphorylation of the Angiotensin Receptor 1
pS346/pS347-AT1 (phospho-Angiotensin Receptor 1...
Serine346/Serine347 (S346/S347) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS346/pS347-AT1 antibody detects phosphorylation in response to agonists. S346/S347 phosphorylation is likely to be involved in...
375.00 € *
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NEW
Agonist-induced Serine335/Threonine336 phosphorylation of the Angiotensin Receptor 1
pS335/pT336-AT1 (phospho-Angiotensin Receptor 1...
Serine335/Threonine336 (S335/T336) is major phosphorylation site of the Angiotensin Receptor 1 (AT1). The pS335/pT336-AT1 antibody detects phosphorylation in response to agonists. S335/T336 phosphorylation is likely to be involved in...
375.00 € *
Details
NEW
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...
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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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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