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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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Citations
KO-Validated
Western blot analysis of Somatostatin Receptor 2 in mouse brain in vivo.
SST2 (non-phospho), Somatostatin Receptor 2...
The non-phospho-SST2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human SST2. It detects selectively the canonical form of SST2 (also referred to as SST2A) and not the putative...
375.00 € *
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Citations
KO-Validated
Immunohistochemical identification of Somatostatin Receptor 2 in human neuroendocrine tumor tissue.
SST2 (IHC-grade), Somatostatin Receptor 2 Antibody
The SST2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human Somatostatin Receptor 2. It detects selectively the canonical form of SST2 (also referred to as SST2A) and not the...
375.00 € *
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NEW
Validation of the Neuropeptide S Receptor in transfected HEK293 cells
NPSR (non-phospho), Neuropeptide S Receptor...
The 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 antibody can also...
375.00 € *
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Citations
KO-Validated
Validation of the VIP Receptor 2 in transfected HEK293 cells
VPAC2 (non-phospho), VIP Receptor 2 Antibody
The VPAC2 antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human VIP receptor 2. It can be used to detect total VPAC2 receptors in Western blots independent of phosphorylation. The VPAC2...
375.00 € *
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Citations
Indentification of the Endothelin Receptor A in mouse tissues.
ETA (non-phospho-Endothelin Receptor A Antibody)
The ETA receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human endothelin receptor A. It can be used to detect ETA receptors in Western blots in a phosphorylation-sensitive manner...
375.00 € *
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Citations
KO-Validated
Immunohistochemical identification of µ-Opioid Receptor in caudate putamen.
MOP (IHC-grade), µ-Opioid Receptor Antibody
The 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. In can be used to...
375.00 € *
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NEW
Validation of the CCR3 Receptor in transfected HEK293 cells
CCR3 (non-phospho), CCR3 Chemokine Receptor...
The non-phospho-CCR3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR3. It can be used to detect total CCR3 receptors in Western blots independent of phosphorylation. The non-phospho-CCR3...
375.00 € *
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NEW
Validation of the CCR1 Receptor in transfected HEK293 cells
CCR1 (non-phospho), CCR1 Chemokine Receptor...
The non-phospho-CCR1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CCR1. It can be used to detect total CCR1 receptors in Western blots independent of phosphorylation. The non-phospho-CCR1...
375.00 € *
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Citations
Validation of the Growth Hormone-Releasing Hormone Receptor in pituitary adenoma.
GHRHR (non-phospho-GHRH Receptor Antibody)
The GHRH receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Growth Hormone-Releasing Hormone Receptor. It detects the canonical form of GHRHR as well as the amino-terminal splice variant SV1. It...
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Citations
Western blot analysis of Somatostatin Receptor 1 in membrane preparations from cells of AtT-20 and BON-1 cell lines.
SST1 (non-phospho-Somatostatin Receptor 1...
The SST1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Somatostatin Receptor 1. It can be used to detect total SST1 receptors in Western blots independent of phosphorylation. The SST1...
375.00 € *
Details
Citations
Validation of the Neurotensin receptor 2 in transfected HEK293 cells.
NTS2 (non-phospho-Neurotensin Receptor 2 Antibody)
The NTS2 antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 2. It can be used to detect total NTS2 receptors in Western blots independent of phosphorylation. The NTS2 antibody can also...
375.00 € *
Details
NEW
Validation of the Proteinase-Activated Receptor 4 in transfected HEK293 cells
PAR4 (non-phospho), Proteinase-Activated...
The non-phospho-PAR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 4. It can be used to detect total PAR4 receptors in Western blots independent of...
375.00 € *
Details
NEW
Indentification of the Endothelin Receptor B in mouse tissues.
ETB (non-phospho-Endothelin Receptor B Antibody)
The non-phospho-ETB receptor antibody is directed against the distal part of the carboxyl-terminal tail of human Endothelin Receptor B (ETB). It can be used to detect total ETB receptors in Western blots independent of phosphorylation....
375.00 € *
Details
NEW
Validation of the 5-Hydroxytryptamine Receptor 6 in transfected HEK293 cells
5-HT6 (non-phospho-5-HT Receptor 6 Antibody)
The non-phospho-5-HT6 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human 5-Hydroxytryptamine Receptor 6 (5-HT6). It can be used to detect total 5-HT6 receptors in Western blots independent of...
375.00 € *
Details
NEW
Validation of the GPR27 Receptor in transfected HEK293 cells
GPR27 (non-phospho), G protein-coupled...
The non-phospho-GPR27 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR27. It can be used to detect total GPR27 receptors in Western blots independent of phosphorylation. The GPR27 antibody...
375.00 € *
Details
NEW
Validation of the GPR25 Receptor in transfected HEK293 cells
GPR25 (non-phospho), G protein-coupled...
The non-phospho-GPR25 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR25. It can be used to detect total GPR25 receptors in Western blots independent of phosphorylation. The GPR25 antibody...
375.00 € *
Details
18 From 28

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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