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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
Immunohistochemical identification of CXC Chemokine Receptor 4 receptor in human lymphoma.
CXCR4 (IHC-grade), CXC Chemokine Receptor 4...
The CXCR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human CXCR4. It can be used to detect CXCR4 receptors in Western blots in a phosphorylation-sensitive manner. After agonist...
CHF400.00 *
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KO-Validated
Validation of the CXC Chemokine Receptor 4 in transfected HEK293 cells
CXCR4 (non-phospho), CXC Chemokine Receptor 4...
The non-phospho-CXCR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human CXCR4. It can be used to detect CXCR4 receptors in Western blots in a phosphorylation-sensitive manner....
CHF400.00 *
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Agonist-induced Serine346/Serine347 phosphorylation of the CXC Chemokine Receptor 4
pS346/pS347-CXCR4 (phospho-CXC Chemokine...
Serine346/serine347 (S346/S347) is a major phosphorylation site of the CXCR4 receptor. The pS346/pS347-CXCR4 antibody detects phosphorylation in response to agonists and after PKC activation. S346/S347 phosphorylation is a key regulator...
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NEW
Validation of the CXCR3 Receptor in transfected HEK293 cells.
CXCR3 (non-phospho), CXCR3 Chemokine Receptor...
The non-phospho-CXCR3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CXCR3. It can be used to detect total CXCR3 receptors in Western blots independent of phosphorylation.
CHF400.00 *
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Validation of the Somatostatin Receptor 3 in transfected HEK293 cells
mSST3 (non-phospho), Somatostatin Receptor 3...
The non-phospho-SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SST3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The non-phospho-SST3...
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NEW
Immunohistochemical identification of Dopamine Receptor 5 in human cortex
D5 (IHC-grade), Dopamine Receptor 5 Antibody
The D5 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human D5. It can be used to detect total D5 receptors in Western blots independent of phosphorylation. The D5 antibody can also be used to...
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NEW
Validation of the Dopamine Receptor 1 in transfected HEK293 cells
D1 (non-phospho-Dopamine Receptor 1 Antibody)
The non-phospho-D1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human D1. It can be used to detect total D1 receptors in Western blots independent of phosphorylation. The non-phospho-D1 antibody...
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Immunohistochemical identification of Bombesin receptor 3 in human ovarian carcinoma.
BB3 (IHC-grade), Bombesin Receptor 3 Antibody
The BB3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Bombesin Receptor 3. It can be used to detect BB3 in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry. It can be...
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Agonist-induced Threonine365/Serine371/Threonine377 phosphorylation of GPR88-Receptor
pT365/pS371/pT377-GPR88 (phospho-GPR88 Antibody)
Threonine365/Serine371/Threonine377 (T365/S371/T377) is a major phosphorylation site of the human GPR88 receptor. The pT365/pS371/pT377-GPR88 antibody detects phosphorylation in response to high-efficacy agonists. T365/S371/T377...
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NEW
Threonine427/Serine429 phosphorylation of the G-protein coupled Receptor 75.
pT427/pS429-GPR75 (phospho-GPR75 Antibody)
Threonine427/Serine429 (T427/S429) is a major phosphorylation site of the human GPR75 receptor. The pT427/pS429-GPR75 antibody detects GRK-mediated constitutive phosphorylation of GPR75 when expressed in HEK293 cells.
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KO-Validated
Immunohistochemical identification of µ-Opioid Receptor in Striatum
MOP (GP-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...
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Citations
Figure 1. Agonist-induced and Agonist-independent Serine363 phosphorylation of the µ-Opioid Receptor
pS363-MOP (phospho-µ-Opioid Receptor Antibody)
Serine363 (S363) is a constitutive phosphorylation site of the µ-opioid receptor (MOP). The pT363-MOP antibody detects phosphorylated MOP in cultured cells. S363 is a substrate for PKC-mediated phosphorylation.
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Agonist-induced Threonine379 phosphorylation of the µ-Opioid Receptor.
pT379-MOP (phospho-µ-Opioid Receptor Antibody)
Threonine379 (T379) is a major phosphorylation site of the µ-opioid receptor (MOP). The pT379-MOP antibody detects phosphorylation in response to high-efficacy agonists but to low-efficacy agonists or after PKC activation. T379...
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Citations
Agonist-induced Threonine376 phosphorylation of the µ-Opioid Receptor.
pT376-MOP (phospho-µ-Opioid Receptor Antibody)
Threonine376 (T376) is a major phosphorylation site of the µ-opioid receptor (MOP). The pT376-MOP antibody detects phosphorylation in response to high-efficacy agonists but to low-efficacy agonists or after PKC activation. T376...
CHF400.00 *
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Citations
Figure 1. Agonist-induced Threonine370 phosphorylation of the µ-opioid receptor.
pT370-MOP (phospho-µ-Opioid Receptor Antibody)
Threonine370 (T370) is a major phosphorylation site of the µ-opioid receptor (MOP). The pT370-MOP antibody detects phosphorylation in response to high-efficacy agonists but to low-efficacy agonists. The pT370-MOP antibody also detects...
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Citations
Figure 1. Agonist-induced Serine375 phosphorylation of the µ-opioid receptor.
pS375-MOP (phospho-µ-Opioid Receptor Antibody)
Serine375 (S375) is the primary phosphorylation site in a hierarchical phosphorylation cascade. The pS375-MOP antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. S375...
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33 From 42

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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