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IL‐4 activates a distinct signal transduction cascade from IL‐3 in factor‐dependent myeloid cells.
Author(s) -
Wang L.M.,
Keegan A.D.,
Paul W.E.,
Heidaran M.A.,
Gutkind J.S.,
Pierce J.H.
Publication year - 1992
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1992.tb05596.x
Subject(s) - biology , signal transduction , microbiology and biotechnology , myeloid , myeloid cells , cancer research , transduction (biophysics) , biochemistry
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.