IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells

EMBO J. 1992 Dec;11(13):4899-908. doi: 10.1002/j.1460-2075.1992.tb05596.x.


Interleukin-4 (IL-4) was shown to induce a potent mitogenic response in the IL-3-dependent myeloid progenitor cell line, FDCP-2. Although IL-4 could not sustain long-term growth of FDCP-2 cells, it enhanced their growth in serum-free medium containing IL-3. IL-4 triggered prominent tyrosine phosphorylation of a substrate(s) migrating at 170 kDa and less striking phosphorylation of several other proteins, including the IL-4 receptor. By contrast, IL-3 induced distinct tyrosine phosphorylation of proteins migrating at 145, 97, 70, 55 and 52 kDa in the same cell line. IL-4 treatment of FDCP-2 cells caused a dramatically strong association of phosphatidylinositol 3-kinase (PI 3-kinase) both with the 170 kDa tyrosine phosphorylated substrate and with the IL-4 receptor itself. By contrast, IL-3 triggered only weak association of PI 3-kinase activity with the 97 kDa substrate. While IL-4 did not affect cellular raf, IL-3 stimulation did induce a shift in its mobility presumably due to serine/threonine phosphorylation. Taken together, our results indicate that IL-4 and IL-3 activate distinct phosphorylation cascades in the same cell background; this may reflect a difference in the biological function of these two cytokines.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • GTPase-Activating Proteins
  • Hematopoietic Stem Cells / metabolism*
  • Interleukin-3 / metabolism*
  • Interleukin-4 / physiology*
  • Mice
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phosphotransferases / metabolism
  • Precipitin Tests
  • Proteins / metabolism
  • Receptors, Interleukin-4
  • Receptors, Mitogen / metabolism
  • Signal Transduction*
  • Substrate Specificity
  • Type C Phospholipases / metabolism
  • Tyrosine / metabolism


  • GTPase-Activating Proteins
  • Interleukin-3
  • Proteins
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Interleukin-4
  • Tyrosine
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinases
  • Type C Phospholipases