Multiple hematopoietic growth factors signal through tyrosine phosphorylation.

The role of tyrosine phosphorylation in the signal transduction of four hematopoietic colony-stimulating factors (IL-3, IL-4, G-CSF, and GM-CSF) in myeloid cells was investigated. In DA-3 cells, both IL-3 and GM-CSF stimulated, within 10 min, the tyrosine phosphorylation of similar proteins with molecular masses of 70, 56, 51, 42, and 38 kD, as well as two different 140-kD proteins, one being the IL-3 receptor. Both of these growth factors were able to increase the transcription, within 1 hr, of two IL-3-inducible genes--c-myc and the gamma chain of the T-cell receptor. In NFS-60 cells, tyrosine phosphorylation on a common 56-kD protein occurred within 10 min in response to either G-CSF or IL-3. In addition, IL-3 stimulation increased the phosphorylation of the 140-kD IL-3 receptor. Both growth factors were able to increase transcription of the c-myc gene within 1 hr. Finally, in NFS-107 cells, IL-3 and IL-4 stimulated the tyrosine phosphorylation, within 10 min, of two different 140-kD proteins, one of which was the IL-3 receptor. Both growth factors were able, within 1 hr, to increase the transcription of the c-myc and gamma chain of the T-cell receptor genes.