Cited by 1,545Cytokine Signaling Pathways and InteractionsT-cell and B-cell ImmunologyReceptor Mechanisms and Signaling

The IL-4 receptor: signaling mechanisms and biologic functions

Nelms, Keats, Keegan, Achsah D., Zamorano, José, Ryan, John J., Paul, William E.·1999·Annual Review of Immunology

Abstract

Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.

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Crossref · 10.1146/annurev.immunol.17.1.701

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Authors
Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E.
Affiliations
National Institutes of Health (US)
Corresponding author
  • Nelms, Keats
  • Paul, William E.
Venue
Annual Review of Immunology
Published
1999-04
Volume
17
Issue
1
Pages
701-738
ISSN
  • 0732-0582 (ISSN-L)
  • 1545-3278
OpenAlex
W2144120552
Cited by
1,545
References
190
Citations by year
2026: 17 · 2025: 27 · 2024: 52 · 2023: 36 · 2022: 54 · 2021: 43 · 2020: 50 · 2019: 44 · 2018: 54 · 2017: 49 · 2016: 52 · 2015: 56 · 2014: 72 · 2013: 52 · 2012: 55
FWCI
6.85
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Immunology (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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
IL-4, IL-4 receptor, common gamma chain, receptor signaling, receptor phosphorylation, cell growth regulation, apoptosis resistance, gene activation, T cell differentiation, cytokine signaling
MeSH terms
Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Phosphoproteins, Signal Transduction, Trans-Activators, Interleukin-4, Protein Tyrosine Phosphatases, Calcium-Calmodulin-Dependent Protein Kinases, Mice, Knockout, Receptors, Interleukin-4, Mitogen-Activated Protein Kinases, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, STAT6 Transcription Factor, Mice, Insulin Receptor Substrate Proteins

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