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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 Bradykinin Receptor 2 in transfected HEK293 cells
B2 (non-phospho-Bradykinin Receptor 2 Antibody)
The non-phospho-B2 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human B2. It can be used to detect total B2 receptors in Western blots independent of phosphorylation. The non-phospho-B2 antibody...
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NEW
Agonist-induced Serine330 phosphorylation of the CXC Chemokine Receptor 4
pS330-CXCR4 (phospho-CXC Chemokine Receptor 4...
Serine330(S330) is a major phosphorylation site of the CXCR4 receptor. The pS330-CXCR4 antibody detects phosphorylation in response to agonists and after PKC activation. S330 phosphorylation is a key regulator of CXCR4 desensitization,...
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Validation of the PACAP Receptor 1 in transfected HEK293 cells
PAC1 (non-phospho), PACAP Receptor 1 Antibody
The PAC1 antibody is directed against the distal end of the carboxyl-terminal tail of human PACAP Receptor 1. It can be used to detect total PAC1 receptors in Western blots independent of phosphorylation. The PAC1 antibody can also be...
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Validation of the Urotensin Receptor in transfected HEK293 cells
UT (non-phospho), Urotensin Receptor Antibody
The UT receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Urotensin Receptor. It can be used to detect total UT receptors in Western blots independent of phosphorylation. The UT antibody can also...
375.00 € *
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Validation of Atypical Chemokine Receptor 4 in transfected HEK293 cells
ACKR4 (non-phospho), Atypical Chemokine...
The ACKR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Atypical Chemokine Receptor 4. It can be used to detect total ACKR4 receptors in Western blots independent of phosphorylation. The...
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Validation of the Cholecystokinin Receptor 2 in transfected HEK293 cells
CCK2 (non-phospho), Cholecystokinin Receptor 2...
The CCK2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Cholecystokinin Receptor 2 (previously called CCKB). It can be used to detect total CCK2 receptors in Western blots independent of...
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Agonist-induced Threonine363 phosphorylation of the κ-Opioid Receptor.
pT363-KOP (phospho-κ-Opioid Receptor Antibody)
Threonine363 is a major phosphorylation site of the kappa-opioid receptor (KOP). The pT363-KOP antibody detects phosphorylation in response to high-efficacy agonists. T363 phosphorylation is a key regulator of KOP desensitization,...
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Agonist-induced Serine356/Threonine357 phosphorylation of the κ-Opioid Receptor.
pS356/pT357-KOP (phospho-κ-Opioid Receptor...
Serine356/Threonine357 is a major phosphorylation site of the kappa-opioid receptor (KOP). The pS356/pT357-KOP antibody detects phosphorylation in response to agonists as well as after PKC activation. S356/T357 phosphorylation is a key...
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Agonist-induced Serine351 phosphorylation of the Nociceptin/Orphanin FQ Receptor.
pS351-NOP (phospho-Nociceptin/Orphanin FQ...
Serine351 (S351) is a major phosphorylation site of the nociceptin/orphanin FQ peptide receptor (NFQ receptor, NOP). The pS351-NOP antibody detects phosphorylation in response to agonists as well as after PKC activation. S351...
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Agonist-induced Serine346 phosphorylation of the Nociceptin/Orphanin FQ Receptor.
pS346-NOP (phospho-Nociceptin/Orphanin FQ...
Serine346 (S346) is a major phosphorylation site of the nociceptin/orphanin FQ peptide receptor (NFQ receptor, NOP). The pS346-NOP antibody detects phosphorylation in response to agonists as well as after PKC activation. S346...
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KO-Validated
Validation of the Nociceptin/Orphanin FQ Receptor in transfected HEK293 cells.
NOP (non-phospho), Nociceptin/Orphanin FQ...
The non-phospho-NFQ receptor (NOP) antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human NOP. It can be used to detect total NOP receptors in Western blots independent of phosphorylation. The...
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Validation of the κ-Opioid Receptor in transfected HEK293 cells.
KOP (non-phospho) κ-Opioid Receptor Antibody
The non-phospho-kappa-opioid receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human KOP. It can be used to detect total KOP receptors in Western blots independent of phosphorylation.
375.00 € *
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SAMPLE PACK
Agonist-induced Serine324/Serine325 phosphorylation of the CXC Chemokine Receptor 4.
CXCR4 Sample Pack (phospho- and...
CXCR4 Sample Pack consisting of all five available phospho- and non-phospho-CXCR4 Antibodies 5 x 20 µL trial size each. Specifically, this sample pack contains the following antibodies pS324/pS325-CXCR4 (7TM0071A), pS330-CXCR4...
300.00 € *
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Agonist-induced Threonine362/Serine363 phosphorylation of the Nociceptin/Orphanin FQ Receptor.
pT362/pS363-NOP (phospho-Nociceptin/Orphanin FQ...
Threonine362/Serine363 (T362/S363) is a major phosphorylation site of the nociceptin/orphanin FQ peptide receptor (NFQ receptor, NOP). The pT362/pS363-NOP antibody detects phosphorylation in response to agonists but not after PKC...
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Agonist-induced Threonine356/Threonine357 phosphorylation of NK1 Receptor
pT356/pT357-NK1 (phospho-Tachykinin Receptor 1...
Threonine356/Threonine357 (T356/T357) is a major phosphorylation site of the NK1 receptor. The pT356/pT357-NK1 antibody detects phosphorylation in response to high-efficacy agonists. T356/T357 phosphorylation is a key regulator of NK1...
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Agonist-induced Serine338/Threonine339 phosphorylation of NK1 Receptor
pS338/pT339-NK1 (phospho-Tachykinin Receptor 1...
Serine338/Threonine339 (S338/T339) is a major phosphorylation site of the NK1 receptor. The pS338/pT339-NK1 antibody detects phosphorylation in response to high-efficacy agonists. S338/T339 phosphorylation is a key regulator of NK1...
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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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