| First Author | Yasuda T | Year | 2007 |
| Journal | Int Immunol | Volume | 19 |
| Issue | 4 | Pages | 487-95 |
| PubMed ID | 17329234 | Mgi Jnum | J:119982 |
| Mgi Id | MGI:3703648 | Doi | 10.1093/intimm/dxm015 |
| Citation | Yasuda T, et al. (2007) Dok-1 and Dok-2 are negative regulators of T cell receptor signaling. Int Immunol 19(4):487-95 |
| abstractText | Interaction of the TCR complex with self- or foreign peptides is a central event in the immune responses. Upon TCR stimulation, a protein-tyrosine kinase (PTK), ZAP-70, is recruited to signaling units of the TCR complex, such as TCRzeta, to play an essential role in T cell activation. Here, we find that mice lacking adaptor proteins Dok-1 and Dok-2 show augmented responses to thymus-dependent, but not thymus-independent, antigens, and that their T cells show elevated responses to TCR stimulation, including the activation of ZAP-70 and subsequent proliferation and cytokine production. Furthermore, the forced expression of Dok-1 or Dok-2 in a CD3(+)CD4(+) T cell clone inhibited the activation of ZAP-70 upon TCR stimulation. Interestingly, the Dok-1 and Dok-2 COOH-terminal moieties bearing the src homology 2 target motifs were dispensable for this negative regulation, even though they are crucial for the known adaptor function of Dok-family proteins. Thus, by an as yet unidentified mechanism, Dok-1 and Dok-2 play an essential role in the negative regulation of TCR signaling. Consistently, all mice lacking these proteins exhibited elevated titers of antibodies to double-stranded DNA and developed lupus-like renal disease. |
