Original Article

Extracellular Signal–regulated Kinase (ERK) Activation by the Pre-T Cell Receptor in Developing Thymocytes In Vivo

Correspondence to: Juan Carlos Zúñiga-Pflücker, Dept. of Immunology, University of Toronto, Medical Sciences Bldg., Toronto, Ontario M5S 1A8, Canada. Tel:416-978-0926 Fax:416-978-1938 E-mail:jc.zuniga.pflucker{at}utoronto.ca.

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.

Key Words: thymus, thymocyte differentiation, cellular signaling, fetal thymic organ culture, pre-TCR

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