Schematic diagram of GM-CSF signal transduction from cell surface to nucleus. GM-CSF binds to the α and β subunits of its cell surface receptor. Two distinct signaling pathways are triggered by GM-CSF: the Ras signaling pathway and the one that involves activation of the Jak2 tyrosine kinase. The first one includes Shc phosphorylation, increases in GTP-bound Ras and activation of mitogen activated (MAP) kinases. The presence of RAS points mutations or the inactivation of neurofibromin (the protein encoded by the neurofibromatosis type 1 gene, NF1 ), constitutively activate the Ras pathway by increasing intracellular levels of Ras-GTP. Modified from Emanuel et al.²³