Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-5 (IL-5) are members of a small but important family of cytokines. These cytokines regulate the survival, proliferation, differentiation and functional activation of blood cells. GM-CSF activity is linked to inflammatory diseases such as asthma and rheumatoid arthritis while in vitro studies have demonstrated that GM-CSF is a growth and survival factor for several myeloid leukaemias including acute and chronic forms of myeloid leukaemia (AML and CML respectively). IL-3 activity is also linked to AML. Through its ability to stimulate eosinophil numbers, survival and activation, IL-5 is widely implicated in allergic inflammation and asthma.
Cytokines act via specific receptor molecules expressed on target cells. The receptors for GM-CSF, IL-3 and IL-5 are expressed on a variety of blood cell types and comprise a cytokine-specific alpha subunit and a shared beta subunit (bc), used by all three cytokines. We recently determined the crystal structure of the GM-CSF:receptor complex (Hansen et al., Cell 134, 496-507, 2008) and from this structure we were able to discern critical details of how the cytokine is able to activate this receptor. We are pursuing studies to expand our knowledge of cytokine receptor function and to discover new agents that can specifically and efficiently block cytokine activity.
Scientists from the Cytokine Receptor Laboratory:
Prof. Angel Lopez, Dr Tim Hercus, Dr Frank Stomski, Dr Hayley Ramshaw, Ms Barbara McClure, Ms Mara Dottore
Collaborators at St. Vincent's Institute of Medical Research:
Prof. Michael Parker, Dr Guido Hansen, Dr Bill McKinstry, Dr Jack King-Scott