Signal transduction by granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors

Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are cytokines which stimulate myeloid bone marrow progenitor cell proliferation and maturation. GM-CSF also enhances the function of terminally differentiated effector cells including neutrophils, monocytes and eosinophils. Both growth factors exhibit similar biological activities on overlapping cell populations which are mediated by high affinity receptors. These receptors share a common beta subunit necessary for signal transduction. The receptors for GM-CSF and IL-3 are members of the hematopoietin receptor superfamily and consequently lack intrinsic tyrosine kinase activity. Several kinases, including JAK2 and raf-1, and other downstream molecules are likely to be responsible for the functional redundancy demonstrated by GM-CSF and IL-3 in factor-responsive cells. This review discusses recent findings which elucidate the signaling pathways activated by these two cytokines.