IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View

Front Immunol. 2018 May 15:9:1037. doi: 10.3389/fimmu.2018.01037. eCollection 2018.

Abstract

In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.

Keywords: IL-4-induced phosphorylated substrate; allergy; insulin receptor substrate; interleukin-13; interleukin-13 receptor alpha1 subunit; interleukin-4; interleukin-4 receptor α; macrophage activation.

Publication types

  • Historical Article
  • Personal Narrative
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Division
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / immunology
  • Insulin Receptor Substrate Proteins / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Receptor, Insulin / history
  • Receptor, Insulin / immunology*
  • Receptors, Interleukin-13 / immunology
  • Receptors, Interleukin-13 / metabolism*
  • Receptors, Interleukin-4 / immunology
  • Receptors, Interleukin-4 / metabolism*
  • Signal Transduction
  • Tyrosine / metabolism
  • U937 Cells

Substances

  • IRS2 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Interleukin-13
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • Interleukin-4
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin