| First Author | Inoue A | Year | 2007 |
| Journal | J Biochem | Volume | 142 |
| Issue | 2 | Pages | 257-63 |
| PubMed ID | 17827176 | Mgi Jnum | J:126539 |
| Mgi Id | MGI:3761555 | Doi | 10.1093/jb/mvm127 |
| Citation | Inoue A, et al. (2007) Dok-1 is a positive regulator of IL-4 signalling and IgE response. J Biochem 142(2):257-63 |
| abstractText | 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 Stat6 and IRS-2, is critical for IL-4 signalling; however, only the activation of Stat6, 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 response. |
