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Cited by 76T-cell and B-cell ImmunologyIron Metabolism and DisordersCytokine Signaling Pathways and Interactions

Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR zeta-chain.

Salmerón, A, Borroto, A, Fresno, M, Crumpton, M J, Ley, S C, Alarcón, B·1995·The Journal of Immunology
DOI 10.4049/jimmunol.154.4.1675
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Abstract

In addition to being an iron transporter, the transferrin receptor (TfR) has been shown to play a role in T cell activation. Stimulation of the TfR with specific Abs results in T cell proliferation, IL-2 secretion, and protein kinase C activation. In this paper we have analyzed early events caused by activation of the TfR. We have found several protein substrates to be tyrosine phosphorylated upon TfR stimulation in the human Jurkat T cell line. Interestingly, the TfR induced tyrosine phosphorylation in cell lines expressing TCR but not in TCR-negative mutants. Restoration of the TCR surface expression in these mutants reestablished the ability of the TfR to induce tyrosine phosphorylation. This result suggests that activation through the TfR is functionally dependent upon the expression of the TCR. Moreover, the functional relationship of the TfR with the TCR complex is also supported by data showing that TfR stimulation resulted in the tyrosine phosphorylation of the TCR zeta-chain; conversely, stimulation of the TCR complex resulted in an increased tyrosine phosphorylation of the TfR. More importantly, the TfR is shown to associate physically with the TCR zeta-chain as well as with the zeta-binding ZAP70 tyrosine kinase. The TfR/zeta complex is expressed on the cell surface independent of the expression of the other subunits of the TCR complex. We suggest that the TfR/zeta complex is responsible for transducing the TfR-induced signals, and that it could serve to amplify signals delivered by Ag binding to the TCR.

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Crossref · 10.4049/jimmunol.154.4.1675

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  • TFR contributes to the signal transduction of TCR stimulation by the direct interaction of the ζ-chains of the CD3 co-receptor, independent of its role in iron uptake.

    “TFR has also been hinted to play a role in T cell activation independent of its role in iron uptake as it also contributes to the signal transduction of TCR stimulation by the direct interaction of the ζ-chains of the CD3 co-receptor (Salmeron et al., 1995).”

    From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Salmeron et al., 1995

  • TfR expression contributes to T cell activation signal transduction following TCR stimulation by direct interaction with ζ-chains of the CD3 co-receptor, independent of its iron functions.

    “Of note, TfR expression has been implicated in T cell activation irrespective of its iron functions, as it also contributes to the signal transduction following TCR stimulation by direct interaction with ζ-chains of the CD3 co-receptor [136].”

    From Iron in immune cell function and host defense (2021) · cites this paper as [136]

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Authors
Salmerón, A., Borroto, A., Fresno, M., Crumpton, M. J., Ley, S. C., & Alarcón, B.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
1995-02
Volume
154
Issue
4
Pages
1675-1683
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.154.4.1675
OpenAlex
W1607180257
Cited by
76
References
0
Citations by year
2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 3
FWCI
2.12
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
transferrin receptor, T cell activation, tyrosine phosphorylation, TCR zeta chain, T cell receptor complex, signal transduction, Jurkat cells, protein kinase C, IL-2 secretion
MeSH terms
Animals, Cell Line, Transformed, Chlorocebus aethiops, Enzyme Activation, Humans, Interleukin-2, Lymphocyte Activation, Membrane Proteins, Phosphorylation, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Receptors, Antigen, T-Cell, Receptors, Transferrin, T-Lymphocytes, Transfection, Tumor Cells, Cultured, Signal Transduction, Lymphoma, T-Cell, ZAP-70 Protein-Tyrosine Kinase

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