Dok-1 is a positive regulator of IL-4 signalling and IgE response

Akane Inoue, Tomoharu Yasuda, Tadashi Yamamoto, Yuji Yamanashi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Interleukin-4 (IL-4) plays an essential role in the control of humoral immunity by regulating lymphocyte proliferation and differentiation, including the T helper type 2 lineage commitment of CD4+ T cells as well as the isotype switching to IgE in B cells. The adaptor protein Dok-1 is known to have an essential role in the negative regulation of a variety of cytokine signalling events. However, here we have found that the loss of Dok-1 impaired the proliferative response of CD4+ T cells and B cells to IL-4. Conversely, the forced expression of Dok-1 in the myeloid cell line 32D augmented the IL-4-induced proliferation, indicating a positive role for Dok-1. Tyrosine phosphorylation, and thereby the activation of State and IRS-2, is critical for IL-4 signalling; however, only the activation of State, not the IRS-2-dependent phosphorylation of Akt, was perturbed in Dok-1-deficient cells stimulated with IL-4. Furthermore, mice lacking Dok-1 showed an impaired IgE response to thymus-dependent antigen. Thus, Dok-1 is a positive regulator of IL-4 signalling and IgE resonse.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalJournal of biochemistry
Volume142
Issue number2
DOIs
Publication statusPublished - Aug 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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