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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
Immunohistochemical identification of Somatostatin Receptor 3 in human growth-hormone-producing pituitary adenoma tissue.
SST3 (IHC-grade), Somatostatin Receptor 3 Antibody
The SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Somatostatin Receptor 3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The SST3...
$ 375.00 *
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Citations
KO-Validated
Immunohistochemical identification of Somatostatin Receptor 3 in neuronal cilia.
mSST3 (IHC-grade), Somatostatin Receptor 3...
The mouse SST3 antibody is directed against the distal end of the carboxyl-terminal tail of mouse and rat Somatostatin Receptor 3. It can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The SST3...
$ 375.00 *
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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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Citations
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 *
Details
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 Tachykinin Receptor 1 in pancreatic carcinoma
NK1 (IHC-grade), Tachykinin Receptor 1 Receptor...
The NK1 antibody is directed against the distal end of the carboxyl-terminal tail of human Tachykinin Receptor 1 (also called Substance P Receptor). It detects selectively the canonical full-length NK1 Tachykinin Receptor. It can be used...
$ 375.00 *
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Citations
KO-Validated
Immunohistochemical identification of CXC Chemokine Receptor 4 in human endometrial carcinoma.
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...
$ 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 *
Details
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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Citations
NEW
KO-Validated
Immunohistochemical Identification of Agonist-induced Threonine379 phosphorylation of the µ-Opioid Receptor in mouse spinal cord
pT379-MOP (IHC-grade phospho-µ-Opioid Receptor...
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...
$ 500.00 *
Details
Citations
KO-Validated
Immunohistochemical identification of Corticotropin-Releasing Factor Receptor 1 in anterior pituitary
CRF1 (IHC-grade), Corticotropin-Releasing...
The CRF1 receptor antibody is directed against the distal part 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 used...
$ 375.00 *
Details
NEW
Immunohistochemical identification of Dopamine Receptor 1 in striatum
D1 (IHC-grade), Dopamine Receptor 1 Antibody
The 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 D1 antibody can also be used to...
$ 375.00 *
Details
Citations
KO-Validated
Immunohistochemical identification of Bradykinin Receptor 2 in pancreatic islets
B2 (IHC-grade), Bradykinin Receptor 2 Antibody
The B2 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human B2. It can be used to detect total B2 receptors in Western blots independent of phosphorylation. The B2 antibody can also be used to...
$ 375.00 *
Details
18 From 28

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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