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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 Threonine428/Serine429 phosphorylation of CRF1 Receptor
pT428/pS429-CRF1...
Threonine428/Serine429 (T428/S429) is a major phosphorylation site of the CRF1 receptor. The pT428/pS429-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. T428/S429 phosphorylation is a key regulator of CRF1...
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NEW
Agonist-induced Threonine431 phosphorylation of CRF1 Receptor
pT431-CRF1 (phospho-Corticotropin-Releasing...
Threonine431 (T431) is a major phosphorylation site of the CRF1 receptor. The pT431-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. T431 phosphorylation is a key regulator of CRF1 desensitization, β-arrestin...
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NEW
Agonist-induced Serine434/Serine437 phosphorylation of CRF1 Receptor
pS434/pS437-CRF1...
Serine434/Serine441 (S437/S441) is a major phosphorylation site of the CRF1 receptor. The pS434/pS437-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. S434/S437 phosphorylation is a key regulator of CRF1...
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pT340-GAL1 (phospho-Galanin Receptor 1 Antibody)
pT340-GAL1 (phospho-Galanin Receptor 1 Antibody)
Threonine340 (T340) is a major phosphorylation site of the GAL1 receptor. The pT340-GAL1 antibody detects phosphorylation in response to high-efficacy agonists. T340 phosphorylation is a key regulator of GAL1 desensitization, β-arrestin...
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NEW
Validation of the Galanin Receptor 1 in transfected HEK293 cells
GAL1 (non-phospho), Galanin Receptor 1 Antibody
The non-phospho-GAL1 receptor antibody is directed against the carboxyl-terminal tail of human GAL1. It can be used to detect total GAL1 receptors in Western blots independent of phosphorylation. The non-phospho-GAL1 antibody can also be...
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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...
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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...
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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...
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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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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...
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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....
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GPR62 (non-phospho), G protein-coupled Receptor 62 Antibody
GPR62 (non-phospho), G protein-coupled...
The non-phospho-GPR62 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR62. It can be used to detect total GPR62 receptors in Western blots independent of phosphorylation. The GPR62 antibody...
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PAR1 (non-phospho), Proteinase-Activated Receptor 1 Antibody
PAR1 (non-phospho), Proteinase-Activated...
The PAR1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 1. It can be used to detect total PAR1 receptors in Western blots independent of phosphorylation. The PAR1...
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Validation of the Atypical Chemokine Receptor 3/CXC Chemokine Receptor 7 in transfected HEK293 cells.
ACKR3 (non-phos, C-Term), Atypical Chemokine...
The non-phospho-ACKR3 receptor antibody is directed against the carboxyl-terminal tail of mouse, rat and human ACKR3/CXCR7. It can be used to detect total ACKR3 receptors in Western blots independent of phosphorylation. The...
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NEW
Validation of the Atypical Chemokine Receptor 3/CXC Chemokine Receptor 7 in transfected HEK293 cells
ACKR3 (non-phos, N-Term), Atypical Chemokine...
The non-phospho-ACKR3 receptor antibody is directed against the amino-terminal tail of mouse, rat and human ACKR3/CXCR7. It can be used to detect total ACKR3 receptors in Western blots independent of phosphorylation. The...
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SAMPLE PACK
Agonist-induced Serine355/Serine360 phosphorylation of the Atypical Chemokine Receptor 3/CXC Chemokine Receptor 7
ACKR3 Sample Pack (phospho- and...
ACKR3 Sample Pack consisting of all four available phospho- and non-phospho-Atypical Chemokine Receptor 3 Antibodies 4 x 20 µL trial size each. Specifically, this sample pack contains the following antibodies pS350/pT352-ACKR3...
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34 From 39

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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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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