An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth

Cell. 1994 Mar 11;76(5):811-20. doi: 10.1016/0092-8674(94)90356-5.


Interleukin-4 (IL-4) treatment of 32D cells overexpressing insulin receptor substrate 1 (IRS-1) causes prompt tyrosine phosphorylation of IRS-1. Transfection of truncation mutants of the human IL-4 (huIL-4) receptor into 32D-IRS-1 cells demonstrated that the region from amino acid 437-557 is important for IL-4 signaling. This region of the IL-4 receptor (IL-4R) contains the motif 488PL-X4-NPXYXSXSD502 (insulin/IL-4R [I4R]) found in the insulin and insulin-like growth factor 1 receptors. Mutation of Y497 to F yielded receptors that caused little or no IRS-1 phosphorylation in response to huIL-4 when expressed in 32D-IRS-1 cells. Most cell lines expressing Y497F also failed to proliferate in response to huIL-4. Furthermore, a glutathione-S-transferase fusion protein containing the I4R motif-bound IRS-1, tyrosine kinase(s), and other unidentified phosphoproteins with molecular sizes of 140, 80, and 55 kd. Thus, the central tyrosine of the I4R motif has a major role in IL-4-mediated signal transduction in 32D cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Consensus Sequence
  • In Vitro Techniques
  • Insulin Receptor Substrate Proteins
  • Molecular Sequence Data
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Interleukin-4
  • Receptors, Mitogen / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Structure-Activity Relationship


  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Phosphoproteins
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Receptor Protein-Tyrosine Kinases