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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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Agonist-induced Serine342 phosphorylation of the Chemokine Receptor 5
pS342-CCR5 (phospho-Chemokine Receptor 5 Antibody)
Serine342 (S342) is a major phosphorylation site of the CCR5 receptor. The pS342-CCR5 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S342 phosphorylation is a key regulator of...
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Agonist-induced Serine336/Serine337 phosphorylation of the Chemokine Receptor 5
pS336/pS337-CCR5 (phospho-Chemokine Receptor 5...
Serine336/Serine337 (S336/S337) is a major phosphorylation site of the CCR5 receptor. The pS336/pS337-CCR5 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. S336/S337...
$ 375.00 *
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Agonist-induced Threonine340 phosphorylation of the Chemokine Receptor 5
pT340-CCR5 (phospho-Chemokine Receptor 5 Antibody)
Threonine340 (T340) is a major phosphorylation site of the CCR5 receptor. The pT340-CCR5 antibody detects phosphorylation in response to high- and low-efficacy agonists and after PKC activation. T340 phosphorylation is a key regulator of...
$ 375.00 *
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Validation of the β2-Adrenoceptor in transfected HEK293 cells
β2 (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...
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Agonist-induced Serine355/Serine356 phosphorylation of the β2 Adrenoceptor
pS355/pS356-β2 (phospho-β2-Adrenoceptor Antibody)
Serine355/Serine356 (S355/S356) is a major phosphorylation site of the β2 adrenoceptor. The pS355/pS356-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S355/S356...
$ 375.00 *
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Agonist-induced Threonine360/Serine364 phosphorylation of the β2 Adrenoceptor
pT360/pS364-β2 (phospho-β2-Adrenoceptor Antibody)
Threonine360/Serine364 (T360/S364) is a major phosphorylation site of the β2 adrenoceptor. The pT360/pS364-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. T360/S364...
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Agonist-induced Serine355 phosphorylation of the β2-Adrenoceptor
pS355-β2 (phospho-β2-Adrenoceptor Antibody)
Serine355 (S355) is a major phosphorylation site of the β2 adrenoceptor. The pS355-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S355 phosphorylation is primarily...
$ 375.00 *
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Agonist-induced Serine356 phosphorylation of the β2-Adrenoceptor
pS356-β2 (phospho-β2-Adrenoceptor Antibody)
Serine356 (S356) is a major phosphorylation site of the β2 adrenoceptor. The pS356-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S356 phosphorylation is primarily...
$ 375.00 *
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NEW
Agonist-induced Threonine360 phosphorylation of the β2-Adrenoceptor
pT360-β2 (phospho-β2-Adrenoceptor Antibody)
Threonine360 (T360) is a major phosphorylation site of the β2 adrenoceptor. The pT360-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. T360 phosphorylation is primarily...
$ 350.00 *
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Agonist-induced Serine364 phosphorylation of the β2-Adrenoceptor
pS364-β2 (phospho-β2-Adrenoceptor Antibody)
Serine364 (S364) is a major phosphorylation site of the β2 adrenoceptor. The pS364-β2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S364 phosphorylation is primarily...
$ 375.00 *
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Agonist-induced Serine355/Serine356 phosphorylation of the β2-Adrenoceptor
β2-Adrenoceptor Sample Pack (phospho- and...
β2-Adrenoceptor Antibody Sample Pack consisting of three phospho- and one non-phospho-β2-Adrenoceptor Antibodies 4 x 20 µL trial size each. Specifically, this sample pack contains the following antibodies pS355/pS356-β2 (7TM0029A),...
$ 300.00 *
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Agonist-induced Threonine306/Threonine310 phosphorylation of the FFA2 Receptor
pT306/pT310-FFA2 (phospho-FFA2 Antibody)
Threonine306/Threonine310 (T306/T310) is major phosphorylation site of the FFA 2 Receptor (FFA2). The pT306/pT310-FFA2 antibody detects phosphorylation in response to agonists. T306/T310 phosphorylation is likely to be involved in...
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Constitutive Serine296/Serine297 phosphorylation of the FFA Receptor 2
pS296/pS297-FFA2 (phospho-FFA2 Antibody)
Serine296/Serine297 (S296/S297) is major phosphorylation site of the FFA Receptor 2 (FFA2). The pS296/pS297-FFA2 antibody detects constitutive phosphorylation of FFA2.
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Agonist-induced Serine358/Threonine360/Serine361 phosphorylation of the CXC Chemokine Receptor 3
pS358/pT360/pS361-CXCR3 (phospho-CXC Chemokine...
Serine358/Threonine360/Serine361 (S358/T360/S361) are a major phosphorylation sites of the CXCR3 receptor. The pS358/pT360/pS361-CXCR3 detects phosphorylation in response to high- and low-efficacy agonists. S358/T360/S361 phosphorylation...
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Agonist-induced Serine343 phosphorylation of GPR183
pS343-GPR183 (phospho-GPR183 Antibody)
Serine343 (S343) is major phosphorylation site of human GPR183 receptor. The pS343-GPR183 antibody detects phosphorylation in response to agonists. S343 phosphorylation is likely to be involved in efficient ligand sequestration by GPR183.
$ 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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1 From 19

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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