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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 CC Chemokine Receptor 7 in human spleen
CCR7 (IHC-grade), CC Chemokine Receptor 7 Antibody
The CCR7 receptor antibody is directed against the distal end of the carboxyl-terminal tail human CCR7. It can be used to detect total CCR7 receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
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KO-Validated
Validation of the µ-Opioid Receptor in transfected HEK293 cells
MOP (GP-non-phospho), µ-Opioid Receptor...
The non-phospho-µ-opioid receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human MOP. It detects selectively the canonical form of MOP and none of the putative splice variants. It can be...
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pT344/pS347-NK1 (IHC-grade phospho-Tachykinin Receptor 1 Antibody)
pT344/pS347-NK1 (IHC-grade phospho-Tachykinin...
Threonine344/Serine347 (T344/S347) is a major phosphorylation site of the NK1 receptor. The pT344/pS347-NK1 antibody detects phosphorylation in response to high-efficacy agonists. T344/S347 phosphorylation is a key regulator of NK1...
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M1 (IHC-grade), M1 Muscarinic Acetylcholine Receptor Antibody
M1 (IHC-grade), M1 Muscarinic Acetylcholine...
The non-phospho-M1 receptor antibody is directed against the 3rd loop of human M1 Muscarinic Acetylcholine Receptor (M1). It can be used to detect total M1 receptors in Western blots independent of phosphorylation. The non-phospho-M1...
375.00 € *
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S1P1 (GP-non-phospho), Sphingosine 1-Phosphate Receptor 1 Antibody, Guinea Pig
S1P1 (GP-non-phospho), Sphingosine 1-Phosphate...
The non-phospho-S1P1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human S1P1. It also detects S1P1 in cultured cells and tissue sections by immunohistochemistry. It can be used to detect total...
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S1P1 (GP-IHC-grade), Sphingosine 1-Phosphate Receptor 1 Antibody, Guinea Pig
S1P1 (GP-IHC-grade), Sphingosine 1-Phosphate...
The non-phospho-S1P1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human S1P1. It also detects S1P1 in cultured cells and tissue sections by immunohistochemistry. It can be used to detect total...
375.00 € *
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pT344/pS347-NK1 (phospho-Tachykinin Receptor 1 Antibody)
pT344/pS347-NK1 (phospho-Tachykinin Receptor 1...
Threonine344/Serine347 (T344/S347) is a major phosphorylation site of the NK1 receptor. The pT344/pS347-NK1 antibody detects phosphorylation in response to high-efficacy agonists. T344/S347 phosphorylation is a key regulator of NK1...
375.00 € *
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Validation of the Neurotensin Receptor 1 in transfected HEK293 cells
NTS1 (GP-non-phospho), Neurotensin Receptor 1...
The NTS1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 1. It can be used to detect total NTS1 receptors in Western blots independent of phosphorylation. The NTS1 antibody...
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Validation of the M1 Muscarinic Acetylcholine Receptor in transfected HEK293 cells
M1 (non-phospho-M1 Muscarinic Acetylcholine...
The non-phospho-M1 receptor antibody is directed against the 3rd loop of human M1 Muscarinic Acetylcholine Receptor (M1). It can be used to detect total M1 receptors in Western blots independent of phosphorylation. The non-phospho-M1...
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S1P1 (IHC-grade), Sphingosine 1-Phosphate Receptor 1 Antibody
S1P1 (IHC-grade), Sphingosine 1-Phosphate...
The non-phospho-S1P1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human S1P1. It also detects S1P1 in cultured cells and tissue sections by immunohistochemistry. It can be used to detect total...
375.00 € *
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NTS1 (GP-IHC-grade), Neurotensin Receptor 1 Antibody, Guinea Pig
NTS1 (GP-IHC-grade), Neurotensin Receptor 1...
The NTS1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 1. It can be used to detect total NTS1 receptors in Western blots independent of phosphorylation. The NTS1 antibody...
375.00 € *
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BLT2 (non-phospho), Leukotriene Receptor BLT2 Antibody
BLT2 (non-phospho), Leukotriene Receptor BLT2...
The non-phospho-BLT2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human BLT2. It can be used to detect total BLT2 receptors in Western blots independent of phosphorylation. The BLT2 antibody can...
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Agonist-induced Serine324/Serine325 phosphorylation of the CXC Chemokine Receptor 4.
pS324/pS325-CXCR4 (phospho-CXC Chemokine...
Serine324/serine325 (S324/S325) is a major phosphorylation site of the CXCR4 receptor. The pS324/pS325-CXCR4 antibody detects phosphorylation in response to agonists but not after PKC activation. S324/S325 phosphorylation is a key...
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NEW
Validation of the GPR75 Receptor in transfected HEK293 cells.
GPR75 (non-phospho), G protein-coupled...
The non-phospho-GPR75 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR75. It can be used to detect total GPR75 receptors in Western blots independent of phosphorylation. The GPR75 antibody...
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Agonist-induced Serine351/Threonine356 phosphorylation of the G-protein coupled Receptor 17
pS351/pT356-GPR17 (phospho-GPR17 Antibody)
Serine351/Threonine356 (S351/T356) is a major phosphorylation site of the human GPR17 receptor. The pS351/pT356-GPR17 antibody detects phosphorylation in response to high-efficacy agonists. S351/T356 phosphorylation is a key regulator of...
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Validation of the Neuropeptide S Receptor in transfected HEK293 cells
NPSR (non-phospho), Neuropeptide S Receptor...
The non-phospho NPSR antibody is directed against the distal end of the carboxyl-terminal tail of human Neuropeptide S Receptor. It can be used to detect total NPS receptors in Western blots independent of phosphorylation. The NPSR...
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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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