The Journal of Experimental Medicine
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Published online 20 August 2001. doi:10.1084/jem.194.4.507
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© The Rockefeller University Press, 0022-1007/2001/8/507/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 4, August 20, 2001 507-518

Original Article

Requirement for Tyrosine Residues 315 and 319 within {zeta} Chain–Associated Protein 70 for T Cell Development

Qian Gonga,b,d, Xiaohua Jina,b, Antonina M. Akka,b, Niko Fogera,b,d, Mike Whitea,c, Guoqing Gonga,b, Julie Bubeck Wardenburga,b, and Andrew C. Chana,b,d

a Center for Immunology, Department of Medicine,
b Division of Rheumatology, Department of Medicine,
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
d Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110
Box 8022, 660 South Euclid Ave., St. Louis, MO 63110.314-454-0175314-362-9011

achan{at}im.wustl.edu

Engagement of the T cell antigen receptor (TCR) induces the transphosphorylation of the {zeta} chain–associated protein of 70,000 Mr (ZAP-70) protein tyrosine kinase (PTK) by the CD4/8 coreceptor associated Lck PTK. Phosphorylation of Tyr 493 within ZAP-70's activation loop results in the enzymatic activation of ZAP-70. Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Phosphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK plays important roles in the generation of second messengers after TCR engagement. Here, we demonstrate that phosphorylation of these two Tyr residues also play important roles in mediating the positive and negative selection of T cells in the thymus.

Key Words: protein tyrosine kinases • signal transduction • T cell activation • lymphocyte development • T cell selection

Abbreviations used in this paper: HA, hemagglutinin; LAT, linker of activated T cell; MFI, mean fluorescence intensity; NF-AT, nuclear factor of activated T cell; PLC{gamma}, phospholipase C {gamma}; PTK, protein Tyr kinase; SH, src homology; Syk, spleen Tyr kinase; Tg, transgene; Tyr, tyrosine; wt, wild-type; ZAP-70, {zeta} chain–associated protein of 70,000 Mr.

© 2001 The Rockefeller University Press


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