SHC PHOSPHORYLATION IN MYELOID CELLS IS REGULATED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, INTERLEUKIN-3, AND STEEL FACTOR AND IS CONSTITUTIVELY INCREASED BY P210(BCR ABL)/

Granulocyte macrophage colony-stimulating factor, interleukin-3, and s teel factor induce proliferation of hematopoietic cells through bindin g to specific, high affinity, cell surface receptors. However, little is known about post-receptor signal transduction pathways. Here we rep ort that an SH2 domain containing protein previously implicated in the activation of p21(ras), Shc, is transiently tyrosine phosphorylated i n myeloid cells after stimulation with granulocyte macrophage colony-s timulating factor, interleukin-3, or steel factor. Also, Shc was found to be constitutively tyrosine phosphorylated in myeloid cell Lines ma de factor independent by expression of p210(BCR/ABL). A Shc-associated 140-kDa protein was identified, which was phosphorylated on tyrosine residues transiently after cytokine stimulation and constitutively aft er expression of p210(BCR/ABL). These findings suggest that She could play an important role in a signal transduction pathway, which leads t o the proliferation of myeloid cells.