Fig. (2) Signalling pathways activated by IL-3 or GM-CSF which are described to impact cell survival are shown. PI3K/AKT: PI3K is activated by ligand binding and converts phosphatidylinositol-4, 5- bisphosphate (PIP2) to phosphatidylinositol-3, 4, 5- triphosphate (PIP3).This recruits both AKT and Protein-dependent kinase 1(PDK1) to the inner membrane surface. AKT is activated by phosphorylation at serine 473 and threonine 308. RAS/RAF activation: After receptor binding by IL-3 or GM-CSF Y577 is phosphorylated and acts as a docking site for Shc and adaptor molecules that results in phosphorylation and activation of the RAS/RAF pathway which ultimately activate the MAP kinases ERK1 and 2. JAK/STAT activation: JAK-2 binds the ßc at Box 1 and is activated by conformation changes in the receptor after ligand binding. JAK-2 acts as a tryosine kinase that activates members of the Signal Transduction and Activators of Transcription family (STATs). These proteins translocate to the nucleus and function as transcription factors. Other pathways are also involved in STAT activation. There is likely to be considerable crosstalk between these pathways and many others not shown may contribute importantly to the regulation of cell survival by cytokine signalling.