The IL-4 receptor: signaling mechanisms and biologic functions

K Nelms; A D Keegan; J Zamorano; J J Ryan; W E Paul

doi:10.1146/annurev.immunol.17.1.701

The IL-4 receptor: signaling mechanisms and biologic functions

Annu Rev Immunol. 1999:17:701-38. doi: 10.1146/annurev.immunol.17.1.701.

Authors

K Nelms¹, A D Keegan, J Zamorano, J J Ryan, W E Paul

Affiliation

¹ Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 10358772
DOI: 10.1146/annurev.immunol.17.1.701

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.

Publication types

Review

MeSH terms

Amino Acid Sequence
Animals
Calcium-Calmodulin-Dependent Protein Kinases / immunology
Humans
Insulin Receptor Substrate Proteins
Interleukin-4 / physiology
Intracellular Signaling Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases*
Molecular Sequence Data
Phosphoproteins / immunology
Protein Tyrosine Phosphatases / immunology
Receptors, Interleukin-4 / chemistry
Receptors, Interleukin-4 / genetics
Receptors, Interleukin-4 / physiology*
STAT6 Transcription Factor
Signal Transduction
Trans-Activators / genetics
Trans-Activators / immunology

Substances

IRS1 protein, human
IRS2 protein, human
Insulin Receptor Substrate Proteins
Intracellular Signaling Peptides and Proteins
Irs1 protein, mouse
Irs2 protein, mouse
Phosphoproteins
Receptors, Interleukin-4
STAT6 Transcription Factor
STAT6 protein, human
Stat6 protein, mouse
Trans-Activators
Interleukin-4
Calcium-Calmodulin-Dependent Protein Kinases
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Protein Tyrosine Phosphatases