Barry, S.Korpelainen, E.Sun, Q.Stomski, F.Moretti, P.Wakao, H.D'Andrea, R.Vadas, M.Lopez, A.Goodall, G.2006-06-252006-06-251997Blood, 1997; 89(3):842-8520006-49711528-0020http://hdl.handle.net/2440/8692Copyright © 1997 by The American Society of HematologyThe 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.enCOS CellsCytoplasmIntracellular FluidAnimalsReceptors, Interleukin-3Antibodies, BlockingAntibodies, MonoclonalSignal TransductionMutagenesisAmino Acid SequenceProtein Structure, TertiaryProtein BindingJournal article0030005050001997091110.1182/blood.v89.3.842A1997WG073000122-s2.0-003090002269056Barry, S. [0000-0002-0597-7609]Lopez, A. [0000-0001-7430-0135]Goodall, G. [0000-0003-1294-0692]