The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1647/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1647-1656

Original Article

Extracellular Signal–Regulated Kinase (Erk) Activation by the Pre-T Cell Receptor in Developing Thymocytes in Vivo

Alison M. Michiea, Sébastien Tropa,b, David L. Wiestc, and Juan Carlos Zúñiga-Pflückera

a Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
b Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada
c Division of Basic Sciences, Immunobiology Working Group, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
Dept. of Immunology, University of Toronto, Medical Sciences Bldg., Toronto, Ontario M5S 1A8, Canada.416-978-1938416-978-0926

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

Abbreviations used in this paper: DLR, DNA loading ratio; DN, double-negative; DP, double-positive; ERK, extracellular signal–regulated kinase; FTOC, fetal thymic organ culture; LAT, linker for activation of T cells; MAPK, mitogen-activated protein kinase; RAG, recombination activating gene; RLUs, relative light units; SLP-76, SH2 domain–containing leukocyte protein, 76 kD; SP, single-positive.

© 1999 The Rockefeller University Press


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