| First Author | Courtney AH | Year | 2017 |
| Journal | Mol Cell | Volume | 67 |
| Issue | 3 | Pages | 498-511.e6 |
| PubMed ID | 28735895 | Mgi Jnum | J:251940 |
| Mgi Id | MGI:6106825 | Doi | 10.1016/j.molcel.2017.06.024 |
| Citation | Courtney AH, et al. (2017) A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45. Mol Cell 67(3):498-511.e6 |
| abstractText | The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck. Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity. |
