A novel type-1 cytokine receptor from fish involved in the Janus kinase/signal transducers and activators of transcription (Jak/STAT) signal pathway

Mol Immunol. 2007 Jul;44(13):3355-63. doi: 10.1016/j.molimm.2007.02.018. Epub 2007 Mar 26.

Abstract

Type I cytokine receptors mediate the action of the members of the long chain cytokines canonically involved in numerous physiological function. Here we report a novel cytokine receptor termed Japanese flounder glycoprotein 130 homologue or JfGPH, exhibiting the unique type I cytokine receptor motifs i.e. having a cytokine binding domain (CBD) containing two pairs of conserved cysteine (C) residues, a WSXWS motif, three fibronectin domains all in the extracellular region. It is also composed of the Jak binding domains Box 1 and Box 2, and a STAT 3 binding motif (Box 3) in the cytoplasmic region suggesting its mediatory role for Janus kinase/Signal transducers and activators of transcription (Jak/STAT) signal pathway. The JfGPH cDNA is about 3kb encoding 801 amino acid residues with a predicted molecular weight of 90kDa and its gene has an 11-exon/10-intron architecture. While JfGPH shows significant homology with the members of type-1 cytokine receptor family including IL6ST (or gp130), IL31alpha (or GLMR), CSF3R (or GCSFR), LIFR, OSMR, IL12Rbeta1 and LEPR, structural and phylogenetic analysis of its protein revealed that it is a novel and an ancestral cytokine receptor found in teleost. JfGPH gene is ubiquitously expressed in Japanese flounder tissues and in a natural embryo (HINAE) cell line showing its critical role in teleost physiological functions similar to gp130 in higher vertebrates. High expression of JfGPH transcripts in immune-related tissues and, in ovary and embryo-derived cell line suggest its role in immune responses, and reproduction/development, respectively. In vitro stimulation of spleen, kidney, peripheral blood leukocytes (PBLs) and HINAE revealed that JfGPH is down-regulated by polyinosinic:polycytidylic acid (poly I:C), an interferon (IFN) inducer, suggesting an apparent control of the JfGPH's expression during IFN-induced Jak/STAT signaling.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • Cytokine Receptor gp130 / chemistry*
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / physiology*
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Flatfishes*
  • Humans
  • Janus Kinases / physiology*
  • Molecular Sequence Data
  • STAT Transcription Factors / physiology*
  • Sequence Homology, Amino Acid*
  • Signal Transduction* / genetics

Substances

  • STAT Transcription Factors
  • Cytokine Receptor gp130
  • Janus Kinases

Associated data

  • GENBANK/AB281273