Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleSpecial Section on Phosphoproteomic Analysis of G Protein-Coupled Pathways - Axelrod Symposium—Minireview
Open Access

Phosphoproteomics-Based Characterization of Prostaglandin E2 Signaling in T Cells

Anna Mari Lone and Kjetil Taskén
Molecular Pharmacology May 2021, 99 (5) 370-382; DOI: https://doi.org/10.1124/molpharm.120.000170
Anna Mari Lone
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital (A.M.L., K.T.) and Institute for Clinical Medicine, University of Oslo, Oslo, Norway (K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anna Mari Lone
Kjetil Taskén
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital (A.M.L., K.T.) and Institute for Clinical Medicine, University of Oslo, Oslo, Norway (K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kjetil Taskén
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Fig. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 1.

    PGE2 signaling regulates phosphorylation of proteins involved in TCR signaling. Phosphosites regulated by PGE2 in the four different phosphoproteomics studies were queried against proteins included in the GO term “T cell receptor signaling pathway” (gray). TCR signaling proteins (green) have phosphosites regulated by PGE2 or one of the EP receptor agonists in one or more of the phosphoproteomics studies. Asterisks indicate proteins not included in GO term TCR signaling (GRAP2 = GADS, NCK1) but known to be involved in TCR signaling and regulated in (Oberprieler et al. 2010)

  • Fig. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 2.

    Overlap in phosphorylation sites regulated in the four studies. Venn diagrams showing the overlap between the four phosphoproteomics studies of PGE2 signaling in T cells. For the (Lone et al., 2021) study, all regulated sites, also from stimulation with individual EP agonists, were included. As evident from this illustration, some of the regulated sites are specific to each study, and some are shared between studies. Left panel does not include de Graaf et al. (2014), which was a targeted study of PKA substrates. Right panel includes all four studies described here.

  • Fig. 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 3.

    Schematic showing kinetics of phosphorylation for phosphosites at different relative positions in a phosphorylation cascade. Phosphorylation time courses may in some cases be used to infer the position of a phosphosite in a signaling pathway, with early phosphorylation suggesting a position near the top of a signaling cascade (red) and later phosphorylation suggesting a position further down in the cascade (blue).

Tables

  • Figures
    • View popup
    TABLE 1

    Current clinical trials with EP4 antagonists.

    This table gives an overview of current clinical trials with EP4 antagonists in cancer. To identify clinical trials, a search was performed on clinicaltrials.gov with the keyword “Prostaglandin E2,” selecting for interventional studies and condition = cancer/neoplasm/tumor. In addition, searches were also performed with the names of all EP4 antagonists listed in the database https://www.guidetopharmacology.org, as well as EP4 antagonists found by searching the NCI Drug Dictionary: https://www.cancer.gov/publications/dictionaries/cancer-drug. Abbreviations: NCI - National Cancer Institute, MSS - microsatellite stable, PD-1 - Programmed death 1, PD-L1 - Programmed Death 1 Ligand 1, NSCLC - Non small-cell lung cancer, DMARD - disease modifying antirheumatic drugs

    Trial NumberTitleConditionsEP4 AntagonistCombination withStatusPhase
    NCT04344795Phase 1a/1b study of TPST-1495 alone and with Pembrolizumab in subjects with solid tumorsSolid tumor, microsatellite stable colorectal cancer, adenocarcinoma of the lung, squamous cell carcinoma of head and neck, bladder cancer, triple-negative breast cancer, gastric cancerTPST-1495PembrolizumabRecruiting1
    NCT03658772Grapiprant and Pembrolizumab in patients with advanced or progressive MSS colorectal cancerMicrosatellite stable colorectal cancerGrapiprantPembrolizumabRecruiting1
    NCT03696212Grapiprant (ARY-007) and Pembrolizumab in patients with advanced or metastatic post-PD-1/L1 NSCLC adenocarcinomaNon–small-cell lung cancer adenocarcinomaGrapiprant andPembrolizumabRecruiting1, 2
    NCT02538432Phase 2 trial of EP4 receptor antagonist AAT-007 (RQ-07; CJ-023,423) in advanced solid tumorsProstate cancer non–small-cell lung cancer breast cancerRQ-00000007GemcitabineWithdrawn2
    NCT03163966A study of the EP4 antagonist CR6086 in combination with methotrexate, in DMARD-naïve patients with early rheumatoid arthritisRheumatoid arthritis, DMARD-naïve. and early disease patientsCR6086MethotrexateUnknown2
    NCT00957983EP4 receptor antagonism and prostaglandin E2 in a human headache modelHeadache, migraineBGC20-1531Completed1, 2
    • View popup
    TABLE 2

    List of phosphoproteomics studies of PGE2 signaling

    The table gives an overview of the studies discussed in this review article. In addition to the four phosphoproteomics studies of PGE2 signaling in T cell, two related articles have also been included. Abbreviations: PMID - PubMed IDentifier, Ti4+ - titanium (IV) ion, IMAC - immobilized metal affinity chromatography.

    StudyCell TypeLabelingEnrichmentData and Pathway Analysis ApproachesNotes
    Oberprieler et al. (2010). High-resolution mapping of prostaglandin E2–dependent signaling networks identifies a constitutively active PKA signaling node in CD8+CD45RO+ T cells. PMID: 20558615Primary CD3+Stable isotope dimethyl labelingPhosphositePlus, NetworKIN, Scansite, Phosida, IceLogoCombined with phosphoflow
    Giansanti et al. (2013). Interrogating cAMP-dependent kinase signaling in Jurkat T cells via a protein kinase A targeted immune-precipitation phosphoproteomics approach. PMID: 23882029JurkatStable isotope dimethyl labelingPKA motif antibody enrichmentIngenuity Pathway Analysis, Cytoscape, STRING, PhosphoSitePlus
    de Graaf et al., 2014. Single-step enrichment by Ti4+-IMAC and label-free quantitation enables in-depth monitoring of phosphorylation dynamics with high reproducibility and temporal Resolution. PMID: 24850871JurkatLabel-freeSTRING, NetworKIN, IceLogo, Gene Ontology analysis
    Lone et al., 2021. Systems approach reveals distinct, joint signaling networks of the four PGE2 receptors in T CellsPrimary CD4+, CD8+, TregsLabel-freeNetworKIN, IceLogo, Phonemes, STRING, PhosphoSitePlus, Predict Functional PhosphositesCombined with phosphoflow
    Individual stimulation of 4 PGE2 receptors
    Gerarduzzi et al. (2014). Quantitative phosphoproteomic analysis of signaling downstream of the prostaglandin E2/G-protein coupled receptor in human synovial fibroblasts: potential antifibrotic networks. PMID: 25223752Primary synovial fibroblastsLabel-freePKA motif antibody enrichmentIngenuity Pathway AnalysisRelated study
    Beltejar et al. (2017). Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells. PMID: 28634298JurkatLabel-freeNetPhorest, Predict Functional Phosphosites, STRING, Gene Ontology AnalysisRelated study.
    Combined stimulation with PDE inhibitors and PGE2
    • View popup
    TABLE 3

    Proteins from GO term T cell receptor signaling pathway whose phosphorylation is regulated by PGE2

    The table shows proteins contained in GO term T cell receptor signaling pathway that have one or more phosphosites that are regulated by PGE2 or one of the EP receptor agonists in one or more of the phosphoproteomics studies reviewed here. Commonly used alternative names for the proteins are shown in parenthesis.

    TCR Signaling ProteinOberprielerGiansantide GraafLoneConditions Regulated in Lone
    BRAF✓
    CARD11 (Carma1)✓✓✓CD8 EP1, EP2, EP3, EP4, PGE2
    CD247 (CD3ζ)✓✓CD8 EP1, EP2, EP3
    CD3E✓
    ELF1✓
    FYB1 (ADAP)✓✓✓CD8 EP2, EP4
    FYN✓CD8 EP2
    GATA3✓
    LCK✓✓✓CD8 EP2 CD4 EP1, EP2, EP3, EP4, PGE2
    LCP2 (SLP76)✓✓CD8 EP2
    LIME1✓CD8 EP1, EP2, EP3, EP4, PGE2
    MAPK1✓
    PLCG1✓✓CD8 PGE2
    PRKD2✓✓✓CD4 EP4
    PTPN22 (LYP)✓✓CD8 EP2
    PTPRC (CD45)✓✓CD8 EP2
    RFTN1✓CD8 EP2
    RNF31✓
    SPN (CD43)✓✓✓CD8 EP1, EP2, EP3, EP4, PGE2 CD4 EP1, EP2, EP3, EP4, PGE2
    TESPA1✓CD8 EP2
    TRAT1 (TRIM)✓
    WNK1✓✓✓CD8 EP2, EP4
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 99 (5)
Molecular Pharmacology
Vol. 99, Issue 5
1 May 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Phosphoproteomics-Based Characterization of Prostaglandin E2 Signaling in T Cells
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleSpecial Section on Phosphoproteomic Analysis of G Protein-Coupled Pathways - Axelrod Symposium—Minireview

PGE2 Signaling in T Cells

Anna Mari Lone and Kjetil Taskén
Molecular Pharmacology May 1, 2021, 99 (5) 370-382; DOI: https://doi.org/10.1124/molpharm.120.000170

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleSpecial Section on Phosphoproteomic Analysis of G Protein-Coupled Pathways - Axelrod Symposium—Minireview

PGE2 Signaling in T Cells

Anna Mari Lone and Kjetil Taskén
Molecular Pharmacology May 1, 2021, 99 (5) 370-382; DOI: https://doi.org/10.1124/molpharm.120.000170
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Phosphoproteomics and Its Application to Signaling Studies
    • Phosphoproteomics Studies of PGE2 Signaling in T Cells
    • PKA Signaling and Interaction with TCR Signaling
    • Non-PKA Signaling Nodes and Pathways
    • Signaling Networks Regulated by PGE2
    • Distinct PGE2 Responses Across T Cell Subtypes
    • Temporal Patterns in PGE2 Signaling
    • Functional Output of PGE2 Signaling in T Cells
    • Perspectives and Future Directions
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Defining a Cellular Map of cAMP Nanodomains
  • Proteomic Analysis of GPCR Cell Biology
Show more Special Section on Phosphoproteomic Analysis of G Protein-Coupled Pathways - Axelrod Symposium—Minireview

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics