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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
Validation of the µ-Opioid Receptor in transfected HEK293 cells
MOP (non-phospho), µ-Opioid Receptor Antibody
The non-phospho-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. It can be...
$ 375.00 *
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Citations
Validation of the Bombesin Receptor 3 in transfected HEK293 cells.
BB3 (non-phospho), 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...
$ 375.00 *
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NEW
Validation of the GPR156 Receptor in transfected HEK293 cells.
GPR156 (non-phospho), G protein-coupled...
The non-phospho-GPR156 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR156. It can be used to detect total GPR156 receptors in Western blots independent of phosphorylation. The GPR156...
$ 375.00 *
Details
NEW
Validation of the ADGRD1/GPR133 Receptor in transfected HEK293 cells
ADGRD1/GPR133 (non-phospho), Adhesion Receptor...
The non-phospho-ADGRD1/GPR133 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human ADGRD1/GPR133. It can be used to detect total ADGRD1/GPR133 receptors in Western blots independent of...
$ 375.00 *
Details
NEW
Validation of the ADGRD1/GPR133 Receptor in transfected HEK293 cells
ADGRD1/GPR133 (GP-non-phospho), Adhesion...
The non-phospho-ADGRD1/GPR133 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human ADGRD1/GPR133. It can be used to detect total ADGRD1/GPR133 receptors in Western blots independent of...
$ 375.00 *
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Rabbit Monoclonal
NEW
Validation of the mGLUR4 Receptor in transfected HEK293 cells
mGLUR4 [UMB18] (RM-non-phospho-Metabotropic...
The non-phospho-mGLUR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human mGLUR4. It can be used to detect total mGLUR4 receptors in Western blots independent of phosphorylation. The mGLUR4...
$ 495.00 *
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NEW
Validation of the CysLT1 Receptor in transfected HEK293 cells
CysLT1 (non-phospho), Leukotriene Receptor...
The non-phospho-CysLT1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human CysLT1. It can be used to detect total CysLT1 receptors in Western blots independent of phosphorylation. The CysLT1...
$ 375.00 *
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Rabbit Monoclonal
NEW
Validation of the Galanin Receptor 1 in transfected HEK293 cells.
GAL1 [UMB14] (RM-non-phospho-Galanin Receptor 1...
The non-phospho-GAL1 antibody is directed against the distal end of the carboxyl-terminal tail of human GAL1. It can be used to detect total GAL1 receptors in Western blots independent of phosphorylation. The GAL1 antibody can also be...
$ 495.00 *
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Rabbit Monoclonal
NEW
Validation of the Galanin Receptor 2 in transfected HEK293 cells
GAL2 [UMB15] (RM-non-phospho-Galanin Receptor 2...
The non-phospho-GAL2 antibody is directed against the distal end of the carboxyl-terminal tail of human GAL2. It can be used to detect total GAL2 receptors in Western blots independent of phosphorylation. The GAL2 antibody can also be...
$ 495.00 *
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Rabbit Monoclonal
NEW
Validation of the Vasopressin Receptor 2 in transfected HEK293 cells.
V2 [UMB16] (RM-non-phospho-Vasopressin Receptor...
The non-phospho-V2 antibody is directed against the distal end of the carboxyl-terminal tail of human V2. It can be used to detect total V2 receptors in Western blots independent of phosphorylation. The V2 antibody can also be used to...
$ 495.00 *
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Rabbit Monoclonal
NEW
Validation of the Vasopressin Receptor 1A in transfected HEK293 cells
V1A [UMB21] (RM-non-phospho-Vasopressin...
The non-phospho-V1A antibody is directed against the distal end of the carboxyl-terminal tail of human V1A. It can be used to detect total V1A receptors in Western blots independent of phosphorylation. The V1A antibody can also be used...
$ 495.00 *
Details
Rabbit Monoclonal
NEW
Validation of the Corticotropin-Releasing Factor Receptor 1 in transfected HEK293 cells
CRF1 [UMB19]...
The non-phospho-CRF1 antibody is directed against the distal end of the carboxyl-terminal tail of human CRF1. It can be used to detect total CRF1 receptors in Western blots independent of phosphorylation. The CRF1 antibody can also be...
$ 495.00 *
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Rabbit Monoclonal
NEW
Validation of the Melanin-Concentrating Hormone Receptor 1 in transfected HEK293 cells.
MCH1 [UMB20]...
The non-phospho-MCH1 antibody is directed against the distal end of the carboxyl-terminal tail of human MCH1. It can be used to detect total MCH1 receptors in Western blots independent of phosphorylation. The MCH1 antibody can also be...
$ 495.00 *
Details
Rabbit Monoclonal
NEW
Validation of the GABAB2 Receptor in transfected HEK293 cells.
GABAB2 [UMB24] (RM-non-phospho-GABAB Receptor 2...
The non-phospho-GABAB2 antibody is directed against the distal end of the carboxyl-terminal tail of human GABAB2 . It can be used to detect total GABAB2 receptors in Western blots independent of phosphorylation. The GABAB2 antibody can...
$ 495.00 *
Details
NEW
Validation of the GPR153 Receptor in transfected HEK293 cells.
GPR153 (non-phospho), G protein-coupled...
The non-phospho-GPR153 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR153. It can be used to detect total GPR153 receptors in Western blots independent of phosphorylation. The GPR153...
$ 375.00 *
Details
NEW
Validation of the mouse GPR62 Receptor in transfected HEK293 cells.
mGPR62 (non-phospho), Mouse G protein-coupled...
The non-phospho-mGPR62 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse GPR62. It can be used to detect total GPR62 receptors in Western blots independent of phosphorylation. The GPR62 antibody...
$ 375.00 *
Details
26 From 43

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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