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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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GPR63 (non-phospho), G protein-coupled Receptor 63 Antibody
GPR63 (non-phospho), G protein-coupled...
The non-phospho-GPR63 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR63. It can be used to detect total GPR63 receptors in Western blots independent of phosphorylation. The GPR63 antibody...
375.00 € *
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GPR63 (IHC-Grade), G protein-coupled Receptor 63 Antibody
GPR63 (IHC-Grade), G protein-coupled Receptor...
The non-phospho-GPR63 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR63. It can be used to detect total GPR63 receptors in Western blots independent of phosphorylation. The GPR63 antibody...
375.00 € *
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Rabbit Monoclonal
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GPER/GPR30 [UMB27] (RM-non-phospho-G Protein-Coupled Estrogen Receptor Antibody), Rabbit Monoclonal
GPER/GPR30 [UMB27] (RM-non-phospho-G...
The non-phospho-GPER/GPR30 antibody is directed against the distal end of the carboxyl-terminal tail of human GPER/GPR30. It can be used to detect total GPER/GPR30 receptors in Western blots independent of phosphorylation. The GPER/GPR30...
495.00 € *
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Rabbit Monoclonal
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GPER/GPR30 [UMB27] (RM-IHC-Grade-G Protein-Coupled Estrogen Receptor Antibody), Rabbit Monoclonal
GPER/GPR30 [UMB27] (RM-IHC-Grade-G...
The non-phospho-GPER/GPR30 antibody is directed against the distal end of the carboxyl-terminal tail of human GPER/GPR30. It can be used to detect total GPER/GPR30 receptors in Western blots independent of phosphorylation. The GPER/GPR30...
495.00 € *
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LPA2 (non-phospho), Lysophosphatidic Acid Receptor 1 Antibody
LPA2 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA2. It can be used to detect total LPA2 receptors in Western blots independent of phosphorylation. The LPA2 antibody can...
375.00 € *
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LPA2 (IHC-Grade), Lysophosphatidic Acid Receptor 1 Antibody
LPA2 (IHC-Grade), Lysophosphatidic Acid...
The non-phospho-LPA2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA2. It can be used to detect total LPA2 receptors in Western blots independent of phosphorylation. The LPA2 antibody can...
375.00 € *
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LPA1 (non-phospho), Lysophosphatidic Acid Receptor 1 Antibody
LPA1 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA1. It can be used to detect total LPA1 receptors in Western blots independent of phosphorylation. The LPA1 antibody can...
375.00 € *
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OR51E1 (IHC-Grade), OR51E1 Antibody
OR51E1 (IHC-Grade), OR51E1 Antibody
The non-phospho-OR51E1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human OR51E1. It can be used to detect total OR51E1 receptors in Western blots independent of phosphorylation. The OR51E1...
375.00 € *
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Validation of the OR51E1 Receptor in transfected HEK293 cells.
OR51E1 (non-phospho), OR51E1 Antibody
The non-phospho-OR51E1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human OR51E1. It can be used to detect total OR51E1 receptors in Western blots independent of phosphorylation. The OR51E1...
375.00 € *
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Validation of the mGLUR5 Receptor in transfected HEK293 cells
mGLUR5 (non-phospho), Metabotropic Glutamate...
The non-phospho-mGLUR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human mGLUR5. It can be used to detect total mGLUR5 receptors in Western blots independent of phosphorylation. The mGLUR5...
375.00 € *
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mGLUR5 (IHC-Grade), Metabotropic Glutamate Receptor 5 Antibody
mGLUR5 (IHC-Grade), Metabotropic Glutamate...
The non-phospho-mGLUR5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human mGLUR5. It can be used to detect total mGLUR5 receptors in Western blots independent of phosphorylation. The mGLUR5...
375.00 € *
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Validation of the Lysophosphatidic Acid Receptor 5 in transfected HEK293 cells.
LPA5 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA5. It can be used to detect total LPA5 receptors in Western blots independent of phosphorylation. The LPA5 antibody can...
375.00 € *
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LPA5 (IHC-Grade), Lysophosphatidic Acid Receptor 5 Antibody
LPA5 (IHC-Grade), Lysophosphatidic Acid...
The non-phospho-LPA5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA5. It can be used to detect total LPA5 receptors in Western blots independent of phosphorylation. The LPA5 antibody can...
375.00 € *
Details
NEW
Validation of the Lysophosphatidic Acid Receptor 3 in transfected HEK293 cells.
LPA3 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA3. It can be used to detect total LPA3 receptors in Western blots independent of phosphorylation. The LPA3 antibody can...
375.00 € *
Details
NEW
LPA3 (IHC-Grade), Lysophosphatidic Acid Receptor 3 Antibody
LPA3 (IHC-Grade), Lysophosphatidic Acid...
The non-phospho-LPA3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA3. It can be used to detect total LPA3 receptors in Western blots independent of phosphorylation. The LPA3 antibody can...
375.00 € *
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NEW
Validation of the GPR162 Receptor in transfected HEK293 cells.
GPR162 (non-phospho), G protein-coupled...
The non-phospho-GPR162 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR162. It can be used to detect total GPR162 receptors in Western blots independent of phosphorylation. The GPR162...
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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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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