Cloning of the low-affinity murine granulocyte-macrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex.

Abstract

A cDNA clone (clone 71) that encodes a low-affinity receptor for murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has been isolated by direct expression. This molecule is the homologue of the human GM-CSF receptor a subunit, although homology between these molecules is surprisingly low (less than 35% amino acid identity). The cDNA encodes a polypeptide of 387 amino acids, which contains the conserved features of the hematopoietin receptor superfamily. When expressed in COS-7 cells, this clone encodes a protein that binds radiolabeled murine GM-CSF with low affinity. Coexpression of clone 71 with a cDNA corresponding to a low-affinity interleukin 3 (IL-3) receptor (AIC2A) did not alter the affinity of binding of either GM-CSF or IL-3. However, coexpression of clone 71 with the IL-3 receptor-related cDNA AIC2B generated high-affinity binding sites for murine GM-CSF but not murine IL-3. These studies show that clone 71 and AIC2B are capable of forming an aj3 complex capable ofbinding murine GM-CSF with high affinity, while AIC2A appears not to be a component of the murine GM-CSF receptor.

CBL Linker Region and RING Finger Mutations Lead to Enhanced Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Signaling via Elevated Levels of JAK2 and LYN

“…In order to mediate its functional activity, GM-CSF binds to its receptor, the GM-CSF receptor (GM-CSFR), 2 consisting of GM-CSR ␣ and GM-CSFR ␤ common (␤c) subunits. The ␤c subunit of the receptor is shared by the IL-3 and IL-5 receptors.…”

“…␤c is the major signaling subunit and is tyrosine-phosphorylated in response to cytokine stimulation. ␤c phosphorylation results in the recruitment of various effectors leading to activation of downstream signaling (2)(3)(4). GM-CSFR ␣ is the major binding subunit, which dictates the binding specificity of the receptor complex for GM-CSF (2,4,5).…”

“…␤c phosphorylation results in the recruitment of various effectors leading to activation of downstream signaling (2)(3)(4). GM-CSFR ␣ is the major binding subunit, which dictates the binding specificity of the receptor complex for GM-CSF (2,4,5). The engagement of GM-CSFR by GM-CSF results in the formation of a dodecameric complex of GM-CSF⅐GM-CSFR ␣⅐GM-CSFR ␤c, which leads to the trans-phosphorylation of GM-CSFR ␤c-associated JAK2 kinases (6).…”

Cross-Talk between ICAM-1 and GM-CSF Receptor Signaling Modulates Eosinophil Survival and Activation

“…Although the GMR␣ subunit is specific for GM-CSF, the GMR␤ subunit (␤ c ) is common to the receptors of GM-CSF, IL-5, and IL-3, which explains some of the overlapping effects of these three cytokines on eosinophils (19). The role of GMR␤ in GM-CSF signaling has been well described (18,20,21). Briefly, following the binding of GM-CSF to GMR␣, subsequent GMR␤ binding converts the interaction to one of high affinity.…”

Enhanced signaling through the IL-2 receptor in CD8+T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+T cells rather than promotion of cell death

“…Differentiated effector CD8 ϩ T cells retain the capacity to secrete many cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF) (17), but do not express the GM-CSF receptor (22). Our laboratory has developed chimeric GM-CSF͞IL-2Rs (GMIL2R) consisting of the ligand-binding ectodomains of the GM-CSF receptor ␣ and ␤ chains fused with the signaling, cytoplasmic endodomains of the IL-2R ␥ and ␤ chains, respectively.…”