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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2204-2210
PLENARY PAPER
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, and
Toshio Kitamura
From the Department of Hematopoietic Factors, the Institute of
Medical Science, the University of Tokyo, Tokyo, Japan; the Department
of Immunology, Tokai University School of Medicine, Isehara, Japan;
Mammalian Genetics Laboratory, Advanced Bioscience Laboratories
(ABL)-Basic Research Program, National Cancer Institute-Frederick
Cancer Research and Development Center, Frederick, MD; and the
Department of Allergy and Rheumatology, Graduate School of Medicine,
the University of Tokyo, Tokyo, Japan.
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 ( 1), was
identified. Although 1 is ubiquitously expressed in multiple
tissues, the expression level is higher in Th2-skewed lymphocytes than
in Th1-skewed ones. The 1 cDNA encodes a 359-amino acid type 1 membrane protein. The extracellular domain of 206 amino acids
showed 24% identity with the murine common  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 1 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 1 alone did not transduce proliferative signals in IL-3-dependent cell lines. However, the membrane-proximal region of 1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that
1 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.
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