| First Author | Wei Q | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 27 | Pages | 15809-15817 |
| PubMed ID | 32571924 | Mgi Jnum | J:291437 |
| Mgi Id | MGI:6444507 | Doi | 10.1073/pnas.1913334117 |
| Citation | Wei Q, et al. (2020) Lck bound to coreceptor is less active than free Lck. Proc Natl Acad Sci U S A 117(27):15809-15817 |
| abstractText | Src family kinase Lck plays critical roles during T cell development and activation, as it phosphorylates the TCR/CD3 complex to initiate TCR signaling. Lck is present either in coreceptor-bound or coreceptor-unbound (free) forms, and we here present evidence that the two pools of Lck have different molecular properties. We discovered that the free Lck fraction exhibited higher mobility than CD8alpha-bound Lck in OT-I T hybridoma cells. The free Lck pool showed more activating Y394 phosphorylation than the coreceptor-bound Lck pool. Consistent with this, free Lck also had higher kinase activity, and free Lck mediated higher T cell activation as compared to coreceptor-bound Lck. Furthermore, the coreceptor-Lck coupling was independent of TCR activation. These findings give insights into the initiation of TCR signaling, suggesting that changes in coreceptor-Lck coupling constitute a mechanism for regulation of T cell sensitivity. |
