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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 Neurotensin Receptor 1 in transfected HEK293 cells
NTS1 (GP-non-phospho), Neurotensin Receptor 1...
The NTS1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Neurotensin Receptor 1. It can be used to detect total NTS1 receptors in Western blots independent of phosphorylation. The NTS1 antibody...
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Immunohistochemical varification of GPR139 Receptor antibody in kidney
GPR139 (IHC-grade), G protein-coupled Receptor...
The non-phospho-GPR139 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR139. It can be used to detect total GPR139 receptors in Western blots independent of phosphorylation. The GPR139...
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Validation of the PAF Receptor in transfected HEK293 cells
PAF (non-phospho), Platelet-Activating Factor...
The non-phospho-PAF receptor antibody is directed against the distal end of the carboxyl-terminal tail of human PAF. It can be used to detect total PAF receptors in Western blots independent of phosphorylation. The PAF antibody can also...
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Immunohistochemical identification of 5-Hydroxytryptamine Receptor 4 in kidney
5-HT4 (IHC-grade), 5-HT Receptor 4 Antibody
The 5-HT4 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human 5-Hydroxytryptamine Receptor 4 (5-HT4). The non-phospho-5-HT4 antibody can also be used to isolate and enrich 5-HT4 receptors from...
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Immunohistochemical varification of 5-Hydroxytryptamine Receptor 2C antibody in Rat Striatum
5-HT2C (IHC-grade), 5-HT Receptor 2C Antibody
The 5-HT2C receptor antibody is directed against the distal part of the carboxyl-terminal tail of human 5-Hydroxytryptamine Receptor 2C (5-HT2C). The non-phospho-5-HT2C antibody can also be used to isolate and enrich 5-HT2C receptors...
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Agonist-induced Serine358/Serine360 phosphorylation of the GPR52 Receptor
pS358/pS360-GPR52 (phospho-GPR52 Antibody)
Serine358/Serine360 (S358/S360) is major phosphorylation site of the GPR52 Receptor (GPR52). The pS358/pS360-GPR52 antibody detects phosphorylation in response to agonists. S358/S360 phosphorylation is likely to be involved in efficient...
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Immunohistochemical identification of XCR Chemokine Receptor 1 in pancreas
XCR1 (IHC-grade), XCR Chemokine Receptor 1...
The non-phospho-XCR1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human XCR1. It can be used to detect total XCR1 receptors in Western blots independent of phosphorylation. The non-phospho-XCR1...
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Validation of the XCR Chemokine Receptor 1 in transfected HEK293 cells
XCR1 (non-phospho), XCR Chemokine Receptor 1...
The non-phospho-XCR1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human XCR1. It can be used to detect total XCR1 receptors in Western blots independent of phosphorylation. The non-phospho-XCR1...
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Validation of the EP3 Prostanoid Receptor in transfected HEK293 cells
EP3 (non-phospho), EP3 Prostanoid Receptor...
The non-phospho-EP3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human EP3. It can be used to detect total EP3 receptors in Western blots independent of phosphorylation.The EP3 antibody can also...
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Immunohistochemical identification of MRGPRX3 Receptor in duodenum
MRGPRX3 (IHC-grade), MRGPRX3 Mas-related...
The non-phospho-MRGPRX3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human MRGPRX3. It can be used to detect total MRGPRX3 receptors in Western blots independent of phosphorylation. The MRGPRX3...
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Validation of the MRGPRX3 Receptor in transfected HEK293 cells
MRGPRX3 (non-phospho), MRGPRX3 Mas-related...
The non-phospho-MRGPRX3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human MRGPRX3. It can be used to detect total MRGPRX3 receptors in Western blots independent of phosphorylation. The MRGPRX3...
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Validation of the Ghrelin Receptor in transfected HEK293 cells
GHSR (non-phospho), Ghrelin Receptor Antibody
The non-phospho-GHSR receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GHSR. It can be used to detect total GHSR receptors in Western blots independent of phosphorylation. The non-phospho-GHSR...
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Validation of the mouse S1P5 Receptor in transfected HEK293 cells
mS1P5 (non-phospho), Mouse Sphingosine...
The non-phospho-mS1P5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouseS1P5. It can be used to detect total mS1P5 receptors in Western blots independent of phosphorylation. The mS1P5 antibody can...
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Validation of the CXCR5 Receptor in transfected HEK293 cells
CXCR5 (non-phospho), CXCR5 Chemokine Receptor...
The non-phospho-CXCR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CXCR5. It can be used to detect total CXCR5 receptors in Western blots independent of phosphorylation.
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Validation of the CXCR2 Receptor in transfected HEK293 cells
CXCR2 (non-phospho), CXCR2 Chemokine Receptor...
The non-phospho-CXCR2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CXCR2. It can be used to detect total CXCR2 receptors in Western blots independent of phosphorylation.
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Immunohistochemical identification of S1P1 Receptor in liver
S1P1 (GP-IHC-grade), Sphingosine 1-Phosphate...
The non-phospho-S1P1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human S1P1. It also detects S1P1 in cultured cells and tissue sections by immunohistochemistry. It can be used to detect total...
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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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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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