JAK1 N-terminus binds to conserved Box 1 and Box 2 motifs of cytokine receptor common β subunit but signal activation requires JAK1 C-terminus

Huei Mei Huang, Ya Li Lee, Ting Wei Chang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The human interleukin-3 receptor (hIL-3R) consists of a unique α subunit (hIL-3Rα) and a common β subunit (βc). Binding of IL-3 to IL-3R activates Janus kinases JAK1 and JAK2. Our previously study showed that JAK2 and JAK1 were constitutively associated with the hIL-3Rα and βc subunits, respectively. In this study, we further demonstrate that JAK2 binds to the intracellular domain of hIL-3Rα and JAK1 binds to the Box 1 and Box 2 motifs of βc using GST-hIL-3R fusion proteins in pull-down assays. JAK1 mutational analysis revealed that its JH7-3 domains bound directly to the Box 1 and Box 2 motifs of βc. We further examined the role of JAK1 JH7-3 domains in JAK1 and JAK2-mediated signaling using the CDJAKs fusion proteins, which consisted of a CD16 extracellular domain, a CD7 transmembrane domain, and either JAK1 (CDJAK1), JAK2 (CDJAK2), or JAK1-JH7-3 domains (CDJAK1-JH7-3) as intracellular domains. Anti-CD16 antibody crosslinking of wild type fusion proteins CDJAK1 with CDJAK2 could mimic IL-3 signaling, however, the crosslinking of fusion proteins CDJAK1-JH7-3 with CDJAK2 failed to activate downstream proteins. These results suggest that the JAK1-JH7-3 domains are required for βc interaction and abolish wild type JAK1 and JAK2-mediated signaling.

Original languageEnglish
Pages (from-to)1078-1084
Number of pages7
JournalJournal of Cellular Biochemistry
Volume99
Issue number4
DOIs
Publication statusPublished - Nov 1 2006

Keywords

  • βc
  • Association
  • Box 1 and Box 2 motifs
  • Fusion proteins
  • GST pull-down
  • hIL-3Rα
  • Intracellular domain
  • JAK1
  • JAK2
  • JH domain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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