Extracellular signal-regulated kinase (ERK) activation by the pre-T cell receptor in developing thymocytes in vivo

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 exp erimental system, we demonstrate that expression of the pre-TCR by developi ng thymocytes induces ERK-1/2 activation within the thymus. In addition, th e activation of this pre-TCR signaling cascade is mediated through Lck. The se findings directly link pre-TCR complex formation with specific downstrea m signaling components in vivo.