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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 Threonine357/Serine360 phosphorylation of the Neuropeptide Y receptor 1
pT357/pS360-NPY1 (phospho-Neuropeptide Y...
Threonine357/Serine360 (T357/S360) is a major phosphorylation site of the Neuropeptide Y Receptor 1. The pT357/pS360-NPY1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
$ 350.00
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Agonist-induced Threonine362/Serine363 phosphorylation of the Neuropeptide Y receptor 1
pT362/pS363-NPY1 (phospho-Neuropeptide Y...
Threonine362/Serine363 (T362/S363) is a major phosphorylation site of the Neuropeptide Y Receptor 1. The pT362/pS363-NPY1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
$ 350.00
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pS353/pT356-CXCR2 (phospho-CXC Chemokine Receptor 2 Antibody)
pS353/pT356-CXCR2 (phospho-CXC Chemokine...
Serine320/Serine321 (S320/S321) is a major phosphorylation site of the CXCR6 receptor. The pS320/pS321-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S320/S321...
$ 350.00
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pS351/pS352-CXCR2 (phospho-CXC Chemokine Receptor 2 Antibody)
pS351/pS352-CXCR2 (phospho-CXC Chemokine...
Serine320/Serine321 (S320/S321) is a major phosphorylation site of the CXCR6 receptor. The pS320/pS321-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S320/S321...
$ 350.00
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pT347-CXCR2 (phospho-CXC Chemokine Receptor 2 Antibody)
pT347-CXCR2 (phospho-CXC Chemokine Receptor 2...
Serine320/Serine321 (S320/S321) is a major phosphorylation site of the CXCR6 receptor. The pS320/pS321-CXCR6 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S320/S321...
$ 350.00
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pT370-BB3 (phospho-Bombesin Receptor 3 Antibody)
pT370-BB3 (phospho-Bombesin Receptor 3 Antibody)
Threonine359/Serine360 (T359/S360) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pT359/pS360-BB2 antibody detects phosphorylation in response to agonists. T359/S360 phosphorylation is likely to be involved in...
$ 350.00
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pT363/pT364-BB3 (phospho-Bombesin Receptor 3 Antibody)
pT363/pT364-BB3 (phospho-Bombesin Receptor 3...
Threonine359/Serine360 (T359/S360) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pT359/pS360-BB2 antibody detects phosphorylation in response to agonists. T359/S360 phosphorylation is likely to be involved in...
$ 350.00
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pT360/pS361-BB3 (phospho-Bombesin Receptor 3 Antibody)
pT360/pS361-BB3 (phospho-Bombesin Receptor 3...
Threonine359/Serine360 (T359/S360) is major phosphorylation site of the Bombesin Receptor 2 (BB2). The pT359/pS360-BB2 antibody detects phosphorylation in response to agonists. T359/S360 phosphorylation is likely to be involved in...
$ 350.00
Details
NEW
Agonist-induced Serine354/Threonine356 phosphorylation of the Neuropeptide Y receptor 2
pS354/pT356-NPY2 (phospho-Neuropeptide Y...
Serine354Threonine356 (S354/T356) is a major phosphorylation site of the Neuropeptide Y Receptor 2. The pS354/pT356-NPY2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
$ 350.00
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Agonist-induced Serine369/Serine374 phosphorylation of the Neuropeptide Y receptor 2
pS369/pS374-NPY2 (phospho-Neuropeptide Y...
Serine369/Serine374 (S369/S374) is a major phosphorylation site of the Neuropeptide Y Receptor 2. The pS369/pS374-NPY2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
$ 350.00
Details
NEW
Agonist-induced Serine351/Serine354 phosphorylation of the Neuropeptide Y
pS351/pS354-NPY2 (phospho-Neuropeptide Y...
Serine351/Serine354 (S351/S354) is a major phosphorylation site of the Neuropeptide Y Receptor 2. The pS351/pS354-NPY2 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
$ 350.00
Details
NEW
Agonist-induced Threonine371 phosphorylation of the TRH1-Receptor
pT371-TRH1 (phospho-Thyrotropin-Releasing...
Threonine371 (T371) is a major phosphorylation site of the TRH1 receptor. The pT371-TRH1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. T371 phosphorylation is primarily...
$ 350.00
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NEW
Agonist-induced Serine364/Threonine365 phosphorylation of the TRH1-Receptor
pS364/pT365-TRH1 (phospho-Thyrotropin-Releasing...
Serine364/Threonine365 (S364/T365) is a major phosphorylation site of the TRH1 receptor. The pS364/pT365-TRH1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S364/T365...
$ 350.00
Details
NEW
Agonist-induced Serine360 phosphorylation of the TRH1-Receptor
pS360-TRH1 (phospho-Thyrotropin-Releasing...
Serine360 (S360) is a major phosphorylation site of the TRH1 receptor. The pS360-TRH1 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S360 phosphorylation is primarily...
$ 350.00
Details
NEW
Agonist-induced Threonine444/Serine447 phosphorylation of the PACAP Receptor 1
pT444/pS447-PAC1 (phospho-PACAP Receptor 1...
Threonine444/Serine447 (T444/S447) is major phosphorylation site of the PACAP Receptor 1 (PAC1). The pT444/pS447-PAC1 antibody detects phosphorylation in response to agonists. T444/S447 phosphorylation is likely to be involved in...
$ 350.00
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Validation of the β1-Adrenoceptor in transfected HEK293 cells
β1 (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...
$ 350.00
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1 From 11

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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