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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 Formylpeptide Receptor 3 in transfected HEK293 cells
FPR3 (non-phospho), Formylpeptide Receptor 3...
The FPR3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Formylpeptide Receptor 3. It can be used to detect total FPR3 receptors in Western blots independent of phosphorylation. The FPR3...
$ 375.00 *
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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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Citations
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...
$ 375.00 *
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NEW
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...
$ 375.00 *
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NEW
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...
$ 375.00 *
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Citations
Validation of the Somatostatin Receptor 3 in transfected HEK293 cells.
SST3 (non-phospho), Somatostatin Receptor 3...
The non-phospho-SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SST3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The non-phospho-SST3...
$ 375.00 *
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Citations
Agonist-induced Serine361 phosphorylation of the Somatostatin Receptor 3
pS361-SST3 (phospho-Somatostatin Receptor 3...
Serine361 (T361) is a major phosphorylation site of the somatostatin receptor 3 (SST3). The pS361-SST3 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S361 phosphorylation is...
$ 375.00 *
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Agonist-induced Threonine333 phosphorylation of the Somatostatin Receptor 5.
pT333-SST5 (phospho-Somatostatin Receptor 5...
Threonine333 (T333) is a major phosphorylation site of the human somatostatin receptor 5 (SST5). The pT333-SST5 antibody detects phosphorylation in response to high-efficacy agonists such as pasireotide but not after activation of PKC....
$ 375.00 *
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Agonist-induced Serine341/Serine343 phosphorylation of the Somatostatin Receptor 2.
pS341/pS343-SST2 (phospho-Somatostatin Receptor...
Serine341/Serine343 (S341/S343) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pS341/pS343-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
$ 375.00 *
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Citations
Agonist-induced Threonine353/Threonine354 phosphorylation of the Somatostatin Receptor 2.
pT353/pT354-SST2 (phospho-Somatostatin Receptor...
Threonine353/Threonine354 (T353/T354) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pT353/pT354-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
$ 375.00 *
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Citations
Agonist-induced Threonine356/Threonine359 phosphorylation of the Somatostatin Receptor 2.
pT356/pT359-SST2 (phospho-Somatostatin Receptor...
Threonine356/Threonine359 (T356/T359) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pT356/pT359-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
$ 375.00 *
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Citations
NEW
Validation of the G protein-coupled Receptor 84 in transfected HEK293 cells
GPR84 (non-phospho), G Protein-Coupled Receptor...
The GPR84 antibody is directed against the distal end of the carboxyl-terminal tail of human GRP84. It can be used to detect total GPR84 receptors in Western blots independent of phosphorylation. The GPR84 antibody can also be used to...
$ 375.00 *
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NEW
Agonist-induced Threonine334/Serine335 phosphorylation of FPR3 Receptor
pT334/pS335-FPR3 (phospho-Formylpeptide...
Threonine334/Serine335 (T334/S335) is a major phosphorylation site of the FPR3 receptor. The pT334/pS335-FPR3 antibody detects phosphorylation in response to high-efficacy agonists. T334/S335 phosphorylation is a key regulator of FPR3...
$ 375.00 *
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NEW
Agonist-induced Threonine337/Threonine339 phosphorylation of FPR3 Receptor
pT337/pT339-FPR3 (phospho-Formylpeptide...
Threonine337/Threonine339 (T337/T339) is a major phosphorylation site of the FPR3 receptor. The pT337/pT339-FPR3 antibody detects phosphorylation in response to high-efficacy agonists. T337/T339 phosphorylation is a key regulator of FPR3...
$ 375.00 *
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NEW
Agonist-induced Threonine335 phosphorylation of FPR2 Receptor
pT335-FPR2 (phospho-Formylpeptide Receptor 2...
Threonine335 (T335) is a major phosphorylation site of the FPR2 receptor. The pT335-FPR2 antibody detects phosphorylation in response to high-efficacy agonists. T335 phosphorylation is a key regulator of FPR2 desensitization, β-arrestin...
$ 375.00 *
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NEW
Agonist-induced Serine338/Threonine339 phosphorylation of Formylpeptide Receptor 1
pS338/pT339-FPR1 (phospho-Formylpeptide...
Serine338/Threonine339 (S338/T339) is a major phosphorylation site of the Formylpeptide Receptor 1 (FPR1). The pS338/pT339-FPR1 antibody detects phosphorylation in response to high-efficacy agonists. S338/T339 phosphorylation is a key...
$ 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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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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