The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15
Open accessAbstract
To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many cytokines bind receptors composed of heterologous polypeptide chains, several of which are shared; a single or combination of two to three JAKs selectively associates with each receptor, and a combination of different STATs can be activated by a single cytokine.
“Many cytokines bind to receptors composed of heterologous polypeptide chains, and several of the polypeptide chains are common or shared. In addition, a single or combination of two to three JAKs selectively associates with each receptor (Lin et al., 1995; Baker et al., 2007; Kiu and Nicholson, 2012) (Fig. 2). The consequence is that a combination of different STATs can be activated by a single cy”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Lin et al., 1995
Cited by
Sorted by citations
Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
Puel, A., Ziegler, S. F., Buckley, R. H., & Leonard., W. J. (1998) · Nature Genetics · doi:10.1038/3877 · Cited by 813 · see citing works
Self-citationEpling-Burnette, P. K., Liu, J. H., Catlett-Falcone, R., Turkson, J., Oshiro, M., Kothapalli, R., Li, Y., Wang, J.-M., Yang-Yen, H.-F., Karras, J., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci9940 · Cited by 633 · see citing works
De novo design of potent and selective mimics of IL-2 and IL-15
Silva, D.-A., Yu, S., Ulge, U. Y., Spangler, J. B., Jude, K. M., Labão-Almeida, C., Ali, L. R., Quijano-Rubio, A., Ruterbusch, M., Leung, I., et al. (2019) · Nature · doi:10.1038/s41586-018-0830-7 · Cited by 531 · see citing works
Interleukin 12: still a promising candidate for tumor immunotherapy?
Lasek, W., Zagożdżon, R., & Jakobisiak, M. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1523-1 · Cited by 495 · see citing works
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
“In addition, a single or combination of two to three JAKs selectively associates with each receptor (Lin et al., 1995; Baker et al., 2007; Kiu and Nicholson, 2012) (Fig.”
BackgroundDehkhoda, F., Lee, C. M. M., Medina, J., & Brooks, A. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00035 · Cited by 304 · see citing works
López-Barrera, D. M., Vázquez-Sánchez, K., Loarca-Piña, M. G. F., & Campos-Vega, R. (2016) · Food Chemistry · doi:10.1016/j.foodchem.2016.05.175 · Cited by 142 · see citing works
Weng, S.-Y., Wang, X., Vijayan, S., Tang, Y., Kim, Y. O., Padberg, K., Regen, T., Molokanova, O., Chen, T., Bopp, T., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.01.028 · Cited by 128 · see citing works
STAT3 positively regulates an early step in B-cell development
Chou, W.-C., Levy, D. E., & Lee, C.-K. (2006) · Blood · doi:10.1182/blood-2006-05-024430 · Cited by 94 · see citing works
- Authors
- Lin, J.-X., Migone, T.-S., Tseng, M., Friedmann, M., Weatherbee, J. A., Zhou, L., Yamauchi, A., Bloom, E. T., Mietz, J., John, S., & Leonard, W. J.
- Affiliations
- National Heart, Lung, and Blood Institute (US)
- R&D Systems (United States) (US)
- Center for Biologics Evaluation and Research (US)
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 2
- Issue
- 4
- Pages
- 331-339
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1995297089
- Cited by
- 752
- References
- 0
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 12 · 2019: 17 · 2018: 15 · 2017: 18 · 2016: 16 · 2015: 8 · 2014: 14 · 2013: 14 · 2012: 12
- FWCI
- 33.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- cytokine redundancy, STAT proteins, STAT5, STAT3, interleukin-2, IL-4, IL-7, IL-13, IL-15, tyrosine phosphorylation, IL-2 receptor beta, IL-7 receptor, IL-4 receptor, peripheral blood lymphocytes, cytokine signaling
- MeSH terms
- Amino Acid Sequence, Base Sequence, Binding, Competitive, DNA-Binding Proteins, Humans, Interleukin-2, Interleukins, Lymphocyte Activation, Lymphocytes, Milk Proteins, Molecular Sequence Data, T-Lymphocytes, DNA Probes, Signal Transduction, Trans-Activators, Interleukin-4, Interleukin-7, Receptors, Interleukin, Interleukin-13, Interleukin-15, STAT5 Transcription Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
