| First Author | Kong MS | Year | 2019 |
| Journal | Sci Signal | Volume | 12 |
| Issue | 567 | PubMed ID | 30723173 |
| Mgi Jnum | J:284383 | Mgi Id | MGI:6380989 |
| Doi | 10.1126/scisignal.aav4373 | Citation | Kong MS, et al. (2019) Inhibition of T cell activation and function by the adaptor protein CIN85. Sci Signal 12(567) |
| abstractText | T cell activation is initiated by signaling molecules downstream of the T cell receptor (TCR) that are organized by adaptor proteins. CIN85 (Cbl-interacting protein of 85 kDa) is one such adaptor protein. Here, we showed that CIN85 limited T cell responses to TCR stimulation. Compared to activated wild-type (WT) T cells, those that lacked CIN85 produced more IL-2 and exhibited greater proliferation. After stimulation of WT T cells with their cognate antigen, CIN85 was recruited to the TCR signaling complex. Early TCR signaling events, such as phosphorylation of zeta-chain-associated protein kinase 70 (Zap70), Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP76), and extracellular signal-regulated kinase (Erk), were enhanced in CIN85-deficient T cells. The inhibitory function of CIN85 required the SH3 and PR regions of the adaptor, which associated with the phosphatase suppressor of TCR signaling-2 (Sts-2) after TCR stimulation. Together, our data suggest that CIN85 is recruited to the TCR signaling complex and mediates inhibition of T cell activation through its association with Sts-2. |
