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

Blood. 2000 Apr 1;95(7):2204-10.

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 (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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cloning, Molecular*
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • Erythropoietin / pharmacology
  • Gene Expression
  • Humans
  • Immunoglobulins
  • Interleukin-3 / physiology
  • Interleukin-4 / physiology
  • Janus Kinase 2
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins*
  • Receptors, Colony-Stimulating Factor / chemistry
  • Receptors, Colony-Stimulating Factor / genetics
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / physiology
  • Sequence Alignment
  • Signal Transduction

Substances

  • CRLF2 protein, human
  • DNA, Complementary
  • Immunoglobulins
  • Interleukin-3
  • Proto-Oncogene Proteins
  • Receptors, Colony-Stimulating Factor
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • Erythropoietin
  • Interleukin-4
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Jak2 protein, mouse
  • Janus Kinase 2