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

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.