Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain

Keishi Fujio, Tetsuya Nosaka, Tetsuo Kojima, Toshiyuki Kawashima, Takashi Yahata, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Kazuhiko Yamamoto, Takashi Nishimura, Toshio Kitamura

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

In a complementary DNA (cDNA) screening of murine Th2-skewed lymphocytes with our recently developed signal sequence trap method termed SST-REX, a novel type 1 cytokine receptor, Delta1 (δ1), was identified. Although δ1 is ubiquitously expressed in multiple tissues, the expression level is higher in Th2-skewed lymphocytes than in Th1-skewed ones. The δ1 cDNA encodes a 359- amino acid type 1 membrane protein. The extracellular domain of 206 amino acids showed 24% identity with the murine common γ receptor that is shared among the receptors for interleukin(IL)-2, IL-4, IL-7, IL-9, and IL-15. The membrane-proximal region of δ1 includes a box1 motif, which is important for association with Janus kinases (JAKs), and showed a significant homology with that of the mouse erythropoietin receptor (EPOR). A box2 motif was also found in close proximity to the box1 region. Dimerization of the cytoplasmic region of δ1 alone did not transduce proliferative signals in IL-3-dependent cell lines. However, the membrane-proximal region of δ1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that δ1 is a subunit of cytokine receptor that may be involved in multiple receptor systems and play a regulatory role in the immune system and hematopoiesis. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2204-2211
Number of pages8
JournalBlood
Volume95
Issue number7
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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