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The GM-CSF, IL-3, and IL-5 receptors constitute the βc family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:α subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures...
The ßc family of cytokines (GM-CSF, IL-3 and IL-5) are largely products of activated T cells and regulate the survival, proliferation, differentiation and functional activation of hematopoietic cells following infection or bleeding. They are variously able to target myeloid hematopoietic stem and progenitor cells as well as mature neutrophils, eosinophils, macrophages and mast cells. Recent evidence...
Interleukin (IL)-3, granulocyte–macrophage colony stimulating factor (GM-CSF) and IL-5 are important cytokines that control production and function of myeloid cells and dendritic cells. Over-expression of these cytokines or their receptors can lead to chronic inflammatory diseases and myeloid leukaemias. These cytokines signal through heterodimeric specific receptors consisting of cytokine-specific...
Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor α chain (IL3Rα) in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5,...
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific α subunit and a βc subunit that is shared with the interleukin (IL)-3...
In the hemopoietic compartment, IL-3, GM-CSF, and IL-5 receptors are major transducers of survival signals; however, the receptor-proximal events that determine this vital function have not been defined. We have found that IL-3 stimulation induces phosphorylation of Ser-585 of β c . This promotes the association of phospho-Ser-585 of β c with 14-3-3 and the p85 subunit of PI 3-K. Mutation...
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