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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 Angiotensin Receptor 1 in transfected HEK293 cells
AT1 (GP-non-phospho) Angiotensin Receptor 1...
The non-phospho-AT1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human Angiotensin Receptor 1 (AT1). It can be used to detect total AT1 receptors in Western blots independent of phosphorylation....
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NEW
Validation of the GPR75 Receptor in transfected HEK293 cells
GPR75 (GP-non-phospho), G protein-coupled...
The non-phospho-GPR75 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human GPR75. It can be used to detect total GPR75 receptors in Western blots independent of phosphorylation. The GPR75 antibody...
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NEW
Validation of the Angiotensin Receptor 1 in transfected HEK293 cells
AT1 (non-phospho-Angiotensin Receptor 1 Antibody)
The non-phospho-AT1 receptor antibody is directed against the distal part of the carboxyl-terminal tail of human Angiotensin Receptor 1 (AT1). It can be used to detect total AT1 receptors in Western blots independent of phosphorylation....
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NEW
Agonist-induced Serine425/Serine429 phosphorylation of VPAC2 Receptor.
pS425/pS429-VPAC2 (phospho-VIP Receptor 2...
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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KO-Validated
Validation of the Somatostatin Receptor 5 in transfected HEK293 cells
SST5 (non-phospho), Somatostatin Receptor 5...
The non-phospho-SST5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SST5. In can be used to detect total SST5 receptors in Western blots independent of phosphorylation. The non-phospho-SST5...
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KO-Validated
Immunohistochemical identification of Somatostatin Receptor 5 in human pancreatic islets
SST5 (IHC-grade), Somatostatin Receptor 5 Antibody
The SST5 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human Somatostatin Receptor 5. In can be used to detect total SST5 receptors in Western blots independent of phosphorylation. The SST5...
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Immunohistochemical identification of Somatostatin Receptor 3 in human neuroendocrine tumor 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...
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Validation of the Somatostatin Receptor 3 in transfected HEK293 cells
SST3 (non-phospho), Somatostatin Receptor 3...
The non-phospho-SST3 receptor antibody is directed against the distal end of the carboxyl-terminal tail of human SST3. In can be used to detect total SST3 receptors in Western blots independent of phosphorylation. The non-phospho-SST3...
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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...
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Agonist-induced Threonine348 phosphorylation of the Somatostatin Receptor 3
pT348-SST3 (phospho-Somatostatin Receptor 3...
Threonine348 (T348) is a major phosphorylation site of the somatostatin receptor 3 (SST3). The pT348-SST3 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation. T348 phosphorylation...
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Agonist-induced Serine337/Threonine341 phosphorylation of the Somatostatin Receptor 3.
pS337/pT341-SST3 (phospho-Somatostatin Receptor...
Serine337/Threonine341 (S337/T341) is a major phosphorylation site of the somatostatin receptor 3 (SST3). The pS337/pT341-SST3 antibody detects phosphorylation in response to high- and low-efficacy agonists but not after PKC activation....
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KO-Validated
Immunohistochemical identification of Somatostatin Receptor 2 in human neuroendocrine tumor tissue
SST2 (IHC-grade), Somatostatin Receptor 2 Antibody
The SST2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human Somatostatin Receptor 2. It detects selectively the canonical form of SST2 (also referred to as SST2A) and not the...
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KO-Validated
Validation of the Somatostatin Receptor 2 in transfected HEK293 cells.
SST2 (non-phospho), Somatostatin Receptor 2...
The non-phospho-SST2 receptor antibody is directed against the distal end of the carboxyl-terminal tail of mouse, rat and human SST2. It detects selectively the canonical form of SST2 (also referred to as SST2A) and not the putative...
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Agonist-induced Threonine356/Threonine359 phosphorylation of the Somatostatin Receptor 2.
pT356/pT359-SST2 (phospho-Somatostatin Receptor...
Threonine356/Threonine359 (T356/T359) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pT356/pT359-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
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Agonist-induced Threonine353/Threonine354 phosphorylation of the Somatostatin Receptor 2.
pT353/pT354-SST2 (phospho-Somatostatin Receptor...
Threonine353/Threonine354 (T353/T354) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pT353/pT354-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
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Agonist-induced Serine341/Serine343 phosphorylation of the Somatostatin Receptor 2.
pS341/pS343-SST2 (phospho-Somatostatin Receptor...
Serine341/Serine343 (S341/S343) is a major phosphorylation site of the somatostatin receptor 2 (SST2). The pS341/pS343-SST2 antibody detects phosphorylation in response to high-efficacy agonists such as octreotide and low-efficacy...
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31 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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