EMERGING PARADIGMS IN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SIGNALING

The myelomonocytic lineage of hematopoiesis is regulated by the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Thi s cytokine has proven to be safe for use in coordination with the trea tments for bone marrow transplants and acute myelogenous leukemia. GM- CSF and related cytokines operate through specific receptors in the me mbranes of target cells of the myelopoietic lineages (both immature an d mature cells). The exact signal transduction mechanisms in the cell are only beginning to be clarified and involve a plethora of signaling molecules. With a wealth of new information from studies in GM-CSF-in duced cell activation, three major experimental approaches are emergin g as gold standards in the exploration of those signaling pathways ini tiated by hematopoietic growth factors. We consider here: (1) a protei n-protein interaction, as exemplified by the association between the c ytokine membrane receptor and JAK kinase; (2) a covalent modification of an enzyme, as studied in the phosphorylation of MAP kinase; and (3) a protein-DNA interaction, as demonstrated by the translocation of ST AT from the cytosol to the nucleus where it can bind to the promoters of specific genes.