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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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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...
$ 375.00 *
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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...
$ 375.00 *
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Citations
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...
$ 375.00 *
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Citations
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...
$ 375.00 *
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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....
$ 375.00 *
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Citations
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...
$ 375.00 *
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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...
$ 375.00 *
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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...
$ 300.00 *
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Citations
Immunohistochemical identification of Parathyroid Hormone Receptor 1 in human kidney.
PTH1 (IHC-grade), Parathyroid Hormone Receptor...
The PTH1 antibody is directed against the distal end of the carboxyl-terminal tail of human Parathyroid Hormone Receptor 1. It can be used to detect total PTH1 receptors in Western blots independent of phosphorylation. The PTH1 antibody...
$ 375.00 *
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Immunohistochemical identification of PACAP Receptor 1 in human neuroendocrine tumor
PAC1 (IHC-grade), PACAP Receptor 1 Antibody
The PAC1 antibody is directed against the distal end of the carboxyl-terminal tail of human PACAP Receptor 1. It can be used to detect total PAC1 receptors in Western blots independent of phosphorylation. The PAC1 antibody can also be...
$ 375.00 *
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Citations
Immunohistochemical identification of VIP Receptor 1 in small intestine.
VPAC1 (IHC-grade), VIP Receptor 1 Antibody
The VPAC1 antibody is directed against the distal end of the carboxyl-terminal tail of human VIP Receptor 1. It can be used to detect total VPAC1 receptors in Western blots independent of phosphorylation. The VPAC1 antibody can also be...
$ 375.00 *
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Citations
KO-Validated
Immunohistochemical identification of VIP Receptor 2 in small intestine.
VPAC2 (IHC-grade), 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...
$ 375.00 *
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Citations
Immunohistochemical identification of Cholecystokinin Receptor 1 in gastric mucosa.
CCK1 (IHC-grade), Cholecystokinin Receptor 1...
The CCK1 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Cholecystokinin Receptor 1 (previously called CCKA). It can be used to detect total CCK1 receptors in Western blots independent of...
$ 375.00 *
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Citations
Immunohistochemical identification of PACAP Receptor 1 in mouse spinal cord dorsal horn.
mPAC1 (IHC-grade), PACAP Receptor 1 Antibody...
The mouse PAC1 antibody is directed against the distal end of the carboxyl-terminal tail of mouse and rat PACAP receptor 1. It can be used to detect total PAC1 receptors in Western blots independent of phosphorylation. The mouse PAC1...
$ 375.00 *
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Citations
NEW
KO-Validated
Immunohistochemical Identification of Agonist-induced Serine375 phosphorylation of the µ-Opioid Receptor in mouse spinal cord
pS375-MOP (IHC-grade phospho-µ-Opioid Receptor...
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...
$ 500.00 *
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Citations
NEW
KO-Validated
Immunohistochemical Identification of Agonist-induced Threonine376 phosphorylation of the µ-Opioid Receptor in mouse spinal cord
pT376-MOP (IHC-grade phospho-µ-Opioid Receptor...
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...
$ 500.00 *
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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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