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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
Validation of the VIP receptor 1 in transfected HEK293 cells
VPAC1 (non-phospho), 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...
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Agonist-induced Serine408/Serine409 phosphorylation of VPAC2 Receptor
pS408/pS409-VPAC2 (phospho-VIP Receptor 2...
Serine408/Serine409 (S408/S409) is a major phosphorylation site of the VPAC2 receptor. The pS408/pS409-VPAC2 antibody detects phosphorylation in response to high-efficacy agonists. S408/S409 phosphorylation is a key regulator of VPAC2...
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Agonist-induced Serine411/Serine415 phosphorylation of VPAC2 Receptor
pS411/pS415-VPAC2 (phospho-VIP Receptor 2...
Serine411/Serine415 (S411/S415) is a major phosphorylation site of the VPAC2 receptor. The pS411/pS415-VPAC2 antibody detects phosphorylation in response to high-efficacy agonists. S411/S415 phosphorylation is a key regulator of VPAC2...
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pS425/pS429-VPAC2 (phospho-VIP Receptor 2 Antibody)
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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Validation of the Cholecystokinin Receptor 1 in transfected HEK293 cells
CCK1 (non-phospho), 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...
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pS417/pS419-CCK1 (phospho-Cholecystokinin Receptor 1 Antibody)
pS417/pS419-CCK1 (phospho-Cholecystokinin...
Serine417/Serine419 (S417/S419) is a major phosphorylation site of the CCK1 receptor. The pS417/pS419-CCK1 antibody detects phosphorylation in response to high-efficacy agonists. S417/S419 phosphorylation is a key regulator of CCK1...
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pS437/pT439-CCK2 (phospho-Cholecystokinin Receptor 2 Antibody)
pS437/pT439-CCK2 (phospho-Cholecystokinin...
Serine437/Threonine439 (S437/T439) is a major phosphorylation site of the CCK2 receptor. The pS437/pT439-CCK2 antibody detects phosphorylation in response to high-efficacy agonists. S437/T439 phosphorylation is a key regulator of CCK2...
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pT427/pS429-CCK2 (phospho-Cholecystokinin Receptor 2 Antibody)
pT427/pS429-CCK2 (phospho-Cholecystokinin...
Threonine427/Serine429 (T427/S429) is a major phosphorylation site of the CCK2 receptor. The pT427/pS429-CCK2 antibody detects phosphorylation in response to high-efficacy agonists. T427/S429 phosphorylation is a key regulator of CRF1...
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Agonist-induced Threonine428/Serine429 phosphorylation of CRF1 Receptor
pT428/pS429-CRF1...
Threonine428/Serine429 (T428/S429) is a major phosphorylation site of the CRF1 receptor. The pT428/pS429-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. T428/S429 phosphorylation is a key regulator of CRF1...
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Agonist-induced Threonine431 phosphorylation of CRF1 Receptor
pT431-CRF1 (phospho-Corticotropin-Releasing...
Threonine431 (T431) is a major phosphorylation site of the CRF1 receptor. The pT431-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. T431 phosphorylation is a key regulator of CRF1 desensitization, β-arrestin...
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Agonist-induced Serine434/Serine437 phosphorylation of CRF1 Receptor
pS434/pS437-CRF1...
Serine434/Serine441 (S437/S441) is a major phosphorylation site of the CRF1 receptor. The pS434/pS437-CRF1 antibody detects phosphorylation in response to high-efficacy agonists. S434/S437 phosphorylation is a key regulator of CRF1...
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pT340-GAL1 (phospho-Galanin Receptor 1 Antibody)
pT340-GAL1 (phospho-Galanin Receptor 1 Antibody)
Threonine340 (T340) is a major phosphorylation site of the GAL1 receptor. The pT340-GAL1 antibody detects phosphorylation in response to high-efficacy agonists. T340 phosphorylation is a key regulator of GAL1 desensitization, β-arrestin...
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Validation of the Galanin Receptor 1 in transfected HEK293 cells
GAL1 (non-phospho), Galanin Receptor 1 Antibody
The non-phospho-GAL1 receptor antibody is directed against the carboxyl-terminal tail of human GAL1. It can be used to detect total GAL1 receptors in Western blots independent of phosphorylation. The non-phospho-GAL1 antibody can also be...
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Citations
KO-Validated
Western blot analysis of Somatostatin Receptor 2 in mouse brain in vivo.
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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Citations
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...
CHF400.00 *
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Citations
KO-Validated
Validation of the VIP Receptor 2 in transfected HEK293 cells
VPAC2 (non-phospho), 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...
CHF400.00 *
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30 From 37

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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