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 steel factor induce proliferation of hematopoietic cells through binding to specific, high affinity, cell surface receptors. However, little is known about post-receptor signal transduction pathways. Here we report that an SH2 domain containing protein previously implicated in the activation of p21^ras, Shc, is transiently tyrosine phosphorylated in myeloid cells after stimulation with granulocyte macrophage colonystimulating factor, interleukin-3, or steel factor. Also, She was found to be constitutively tyrosine phosphorylated in myeloid cell lines made 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 after expression of p210^BCR/ABL. These findings suggest that Shc could play an important role in a signal transduction pathway, which leads to the proliferation of myeloid cells.