| First Author | Lovatt M | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 22 | Pages | 8655-65 |
| PubMed ID | 16966372 | Mgi Jnum | J:114668 |
| Mgi Id | MGI:3689682 | Doi | 10.1128/MCB.00168-06 |
| Citation | Lovatt M, et al. (2006) Lck Regulates the Threshold of Activation in Primary T Cells, While both Lck and Fyn Contribute to the Magnitude of the Extracellular Signal-Related Kinase Response. Mol Cell Biol 26(22):8655-65 |
| abstractText | The src family kinases p56(lck) (Lck) and p59(fyn) (Fyn) are the most proximal signaling molecules to be activated downstream of the T-cell receptor. Using an inducible transgenic model, we can regulate the expression of Lck in primary T cells and ask how the signaling cascade and differentiation potential are affected by the absence or the presence of reduced levels of Lck. We show that in naive T cells, Lck controls the threshold of activation by preferentially regulating multiple signaling pathways that result in the mobilization of Ca(2+) through activation of phospholipase C-gamma and protein kinase C as well as activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. Fyn is also able to stimulate the ERK/MAPK pathway in primary T cells but has little influence on the mobilization of Ca(2+). Only Lck efficiently stimulates production of diacylglycerol and therefore RasGRP1 recruitment to the plasma membrane and phosphorylation of Shc, suggesting that Fyn activates ERK via a different upstream signaling route. Finally, we show that signals through Lck are essential for the development of T-cell-effector potential, particularly for effective cytokine transcription. |
