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

Immunity. 1995 Apr;2(4):331-9. doi: 10.1016/1074-7613(95)90141-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding, Competitive
  • DNA Probes
  • DNA-Binding Proteins / biosynthesis*
  • Humans
  • Interleukin-13 / pharmacology*
  • Interleukin-15
  • Interleukin-2 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Interleukin-7 / pharmacology*
  • Interleukins / pharmacology*
  • Lymphocyte Activation
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Milk Proteins*
  • Molecular Sequence Data
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Trans-Activators / biosynthesis*

Substances

  • DNA Probes
  • DNA-Binding Proteins
  • Interleukin-13
  • Interleukin-15
  • Interleukin-2
  • Interleukin-7
  • Interleukins
  • Milk Proteins
  • Receptors, Interleukin
  • STAT5 Transcription Factor
  • Trans-Activators
  • Interleukin-4