IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells.
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.
Wang
L M
LM
Laboratory of Cellular and Molecular Biology, NCI, NIH, Bethesda, MD.
Keegan
A D
AD
Paul
W E
WE
Heidaran
M A
MA
Gutkind
J S
JS
Pierce
J H
JH
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D020690:GTPase-Activating Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism*; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D020690:GTPase-Activating Proteins; D007377:Interleukin-3; D011506:Proteins; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D014443:Tyrosine; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases