Clarification of the role of N-glycans on the common beta-subunit of the human IL-3, IL-5 and GM-CSF receptors and the murine IL-3 beta-receptor in ligand-binding and receptor activation

Murphy, JM; Soboleva, TA; Mirza, S; Ford, SC; Olsen, JE; Chen, JL; Young, IG

Author(s): Murphy, JM; Soboleva, TA; Mirza, S; Ford, SC; Olsen, JE; Chen, JL; Young, IG;
Details: Publication Year 2008-05,Volume 42,Issue #2,Page 234-242
Journal Title: CYTOKINE
Publication Type: Journal Article
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 are related cytokines that play key roles in regulating the differentiation, proliferation, survival and activation of myeloid blood cells. The cell surface receptors for these cytokines are composed of cytokine-specific alpha-subunits and a common P-receptor (Pc), a shared subunit that is essential for receptor signaling in response to GM-CSF, IL-3 and IL-5. Previous studies have reached conflicting conclusions as to whether N-glycosylation of the beta c-subunit is necessary for functional GM-CSF, IL-3 and IL-5 receptors. We sought to clarify whether beta c N-glycosylation plays a role in receptor function, since all structural studies of human Pc to date have utilized recombinant protein lacking N-glycosylation at Asn(328). Here, by eliminating individual N-glycans in human beta c and the related murine homolog, beta(IL-3), we demonstrate unequivocally that ligand-binding and receptor activation are not critically dependent on individual N-glycosylation sites within the P-subunit although the data do not preclude the possibility that N-glycans may exert some sort of fine control. These studies support the biological relevance of the X-ray crystal structures of the human Pc domain 4 and the complete ectodomain, both of which lack N-glycosylation at Asn(328). (C) 2008 Elsevier Ltd. All rights reserved.
Publisher: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
Keywords: COLONY-STIMULATING FACTOR; HIGH-AFFINITY BINDING; COMPLETE EXTRACELLULAR DOMAIN; MOUSE INTERLEUKIN-3 IL-3; GLYCOSYLATION SITES; SIGNAL-TRANSDUCTION; EXPRESSION CLONING; MOLECULAR-CLONING; ALPHA-CHAIN; AMINO-ACID
Publisher's Version: https://doi.org/10.1016/j.cyto.2008.02.010
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Creation Date: 2008-05-01 12:00:00