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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 Threonine348/Serine350 phosphorylation of MCH1 Receptor
pT348/pS350-MCH1 (phospho-Melanin-Concentrating...
Threonine348/Serine350 (T348/S350) is a major phosphorylation site of the MCH1 receptor. The pT348/pS350-MCH1 antibody detects phosphorylation in response to high-efficacy agonists. T348/S350 phosphorylation is a key regulator of MCH1...
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NEW
Agonist-induced Threonine335/Serine338 phosphorylation of MCH2 Receptor
pT335/pS338-MCH2 (phospho-Melanin-Concentrating...
Threonine335/Serine338 (T335/S338) is a major phosphorylation site of the MCH2 receptor. The pT335/pS338-MCH2 antibody detects phosphorylation in response to high-efficacy agonists. T335/S338 phosphorylation is a key regulator of MCH2...
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NEW
Immunohistochemical identification of Proteinase-Activated Receptor 4 in Small Intestine
PAR4 (IHC-Grade), Proteinase-Activated Receptor...
The non-phospho-PAR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 4. It can be used to detect total PAR4 receptors in Western blots independent of...
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NEW
Validation of the Proteinase-Activated Receptor 4 in transfected HEK293 cells
PAR4 (non-phospho), Proteinase-Activated...
The non-phospho-PAR4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Proteinase-Activated Receptor 4. It can be used to detect total PAR4 receptors in Western blots independent of...
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NEW
Immunohistochemical identification of CC Chemokine Receptor 7 in human spleen
CCR7 (IHC-grade), CC Chemokine Receptor 7 Antibody
The CCR7 receptor antibody is directed against the distal end of the carboxyl-terminal tail human CCR7. It can be used to detect total CCR7 receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
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NEW
Validation of the CC Chemokine Receptor 7 in transfected HEK293 cells
CCR7 (non-phospho), CC Chemokine Receptor 7...
The CCR7 receptor antibody is directed against the distal end of the carboxyl-terminal tail human CCR7. It can be used to detect total CCR7 receptors in Western blots independent of phosphorylation. It can also be used to isolate and...
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NEW
Indentification of EP4 Receptor in mouse tissues
EP4 (GP-non-phospho), EP4 Prostanoid Receptor...
The non-phospho-EP4 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human EP4. It can be used to detect total EP4 receptors in Western blots independent of phosphorylation.
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NEW
Validation of the Formylpeptide Receptor 2 in transfected HEK293 cells
FPR2 (GP-non-phospho), Formylpeptide Receptor 2...
The FPR2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Formylpeptide Receptor 2. It can be used to detect total FPR2 receptors in Western blots independent of phosphorylation. The FPR2...
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NEW
Validation of the Lysophosphatidic Acid Receptor 3 in transfected HEK293 cells.
LPA3 (non-phospho), Lysophosphatidic Acid...
The non-phospho-LPA3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human LPA3. It can be used to detect total LPA3 receptors in Western blots independent of phosphorylation. The LPA3 antibody can...
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Citations
KO-Validated
Validation of the µ-Opioid Receptor in transfected HEK293 cells
MOP (GP-non-phospho), µ-Opioid Receptor...
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...
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Validation of the Atypical Chemokine Receptor 3 in transfected HEK293 cells
ACKR3 (GP-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. It can be used to detect total ACKR3 receptors in Western blots independent of phosphorylation. The non-phospho-ACKR3...
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NEW
Validation of the GPR119 Receptor in transfected HEK293 cells
GPR119 (non-phospho), G protein-coupled...
The non-phospho-GPR119 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR119. It can be used to detect total GPR119 receptors in Western blots independent of phosphorylation. The GPR119...
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Immunohistochemical identification of Serine 425/Serine429 phosphorylation of VPAC2 Receptor in mouse brain suprachiasmatic nucleus.
pS425/pS429-VPAC2 (IHC-grade phospho-VIP...
Serine425/Serine429 (S425/S429) is a major phosphorylation site of the VPAC2 receptor. The pS425/pS429-VPAC2 antibody detects phosphorylation in response to high-efficacy agonists. S425/S429 phosphorylation is a key regulator of VPAC2...
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SAMPLE PACK
Agonist-induced Serine324/Serine325 phosphorylation of the CXC Chemokine Receptor 4.
CXCR4 Sample Pack (phospho- and...
CXCR4 Sample Pack consisting of all five available phospho- and non-phospho-CXCR4 Antibodies 5 x 20 µL trial size each. Specifically, this sample pack contains the following antibodies pS324/pS325-CXCR4 (7TM0071A), pS330-CXCR4...
CHF300.00 *
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NEW
Validation of the Corticotropin-Releasing Factor Receptor 1 in transfected HEK293 cells
CRF1 (non-phospho-Corticotropin-Releasing...
The non-phospho-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 non-phospho-CRF1...
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NEW
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...
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25 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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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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