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.


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*


  • 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