title: Roles of the N and C terminal domains of the interleukin-3 receptor alpha chain in receptor function.
abstract: The interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 receptor alpha chains are each composed of three extracellular domains, a transmembrane domain and a short intracellular region. Domains 2 and 3 constitute the cytokine receptor module (CRM), typical of the cytokine receptor superfamily; however, the function of the N-terminal domain is not known. We have investigated the functions of the N-terminal and C-terminal domains of the IL-3 receptor (IL-3R) alpha chain. We find that cells transfected with the receptor beta chain (h beta c) and a truncated IL-3R alpha that is devoid of the intracellular region fail to proliferate or to activate STAT5 in response to human IL-3, despite binding the IL-3 with affinity indistinguishable from that of full-length receptor. In addition, IL-3-induced phosphorylation of h beta c was not detected. Thus, the IL-3R alpha intracellular region does not contribute detectably to stabilization of the receptor/ligand complex, but is essential for signal propagation. In contrast, a truncated IL-3R alpha with the N-terminal domain deleted interacts functionally with the beta chain; mouse cells transfected with these receptor chains proliferate in response to human IL-3 and STAT5 transcription factor is activated. High- and low-affinity binding sites are retained, although the affinity for IL-3 is decreased 15-fold, indicating a significant role for the N-terminal domain in IL-3 binding.
authors.affiliation: Hanson Centre for Cancer Research, Adelaide, Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Barry
authors.forename: E
authors.initials: E
authors.lastname: Korpelainen
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.forename: F C
authors.initials: FC
authors.lastname: Stomski
authors.forename: P A
authors.initials: PA
authors.lastname: Moretti
authors.forename: H
authors.initials: H
authors.lastname: Wakao
authors.forename: R J
authors.initials: RJ
authors.lastname: D'Andrea
authors.forename: M A
authors.initials: MA
authors.lastname: Vadas
authors.forename: A F
authors.initials: AF
authors.lastname: Lopez
authors.forename: G J
authors.initials: GJ
authors.lastname: Goodall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019556:COS Cells; D003593:Cytoplasm / Q000737:chemistry / Q000502:physiology; D007424:Intracellular Fluid / Q000737:chemistry / Q000502:physiology; D016296:Mutagenesis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016185:Receptors, Interleukin-3 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016185:Receptors, Interleukin-3