Extracellular signal-regulated kinase (ERK) activation by the pre-T cell receptor in developing thymocytes in vivo: Journal of Experimental Medicine

The first checkpoint in T cell development occurs between the CD4^-CD8^- and CD4⁺CD8⁺ stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal-regulated kinases (ERKs)- 1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK- 1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo.