MECHANISM OF ACTIVATION OF THE GM-CSF IL-3, AND IL-5 FAMILY OF RECEPTORS

The process of ligand binding leading to receptor activation is an ord ered and sequential one. High-affinity binding of GM-CSF, interleukin 3 (IL-3), and IL-5 to their receptors induces a number of key events a t the cell surface and within the cytoplasm that are necessary for rec eptor activation. These include receptor oligomerization, activation o f tyrosine kinase activity, phosphorylation of the receptor, and the r ecruitment of SH2 (src-homology) and PTB (phosphotyrosine binding) dom ain proteins to the receptor. Such a sequence of events represents a r ecurrent theme among cytokine, growth factor, and hormone receptors; h owever, a number of very recent and interesting findings have identifi ed unique features in this receptor system in terms of: A) how GM-CSF/ IL-3/IL-5 bind, oligomerize, and activate their cognate receptors; B) how multiple biological responses such as proliferation, survival, and differentiation can be transduced from activated GM-CSF, IL-3, or IL- 5 receptors, and C) how the presence of novel phosphotyrosine-independ ent signaling motifs within a specific cytoplasmic domain of pc may be important for mediating survival and differentiation by these cytokin es, This review does not attempt to be all-encompassing but rather to focus on the most recent and significant discoveries that distinguish the GM-CSF/IL-3/IL-5 receptor subfamily from other cytokine receptors.