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 (delta1), was identified. Although delta1 is ubiquitously expressed in multiple tissues, the expression level is higher in Th2-skewed lymphocytes than in Th1-skewed ones. The delta1 cDNA encodes a 359-amino acid type 1 membrane protein. The extracellular domain of 206 amino acids showed 24% identity with the murine common gamma 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 delta1 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 delta1 alone did not transduce proliferative signals in IL-3-dependent cell lines. However, the membrane-proximal region of delta1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that delta1 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.
Fujio
K
K
Department of Hematopoietic Factors, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Nosaka
T
T
Kojima
T
T
Kawashima
T
T
Yahata
T
T
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Yamamoto
K
K
Nishimura
T
T
Kitamura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004921:Erythropoietin / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D053614:Janus Kinase 2; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment; D015398:Signal Transduction
C498762:CRLF2 protein, human; D018076:DNA, Complementary; D007136:Immunoglobulins; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D004921:Erythropoietin; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2