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© The Rockefeller University Press, 0022-1007/2000/2/703/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 4, February 21, 2000 703-716

Original Article

Lck Domains Differentially Contribute to Pre–T Cell Receptor (Tcr)–And TCR-{alpha}/β–Regulated Developmental Transitions

Kui Lina,b, Nancy S. Longoa, Xin Wanga, Judy A. Hewitta, and Kristin M. Abrahama,b

a Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201
b Graduate Program in Molecular and Cellular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201
Department of Microbiology and Immunology, BRB 13-045, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201-1559.410-706-2129410-706-4126

kabraham{at}umaryland.edu

Maturational changes at the CD4–CD8– double negative (DN) to CD4+CD8+ double positive (DP) transition are dependent on signals generated via the pre–T cell receptor (TCR) and the nonreceptor protein tyrosine kinase p56lck (Lck). How Lck activities are stimulated or relayed after pre-TCR formation remains obscure. Our structure–function mapping of Lck thymopoietic properties reveals that the noncatalytic domains of Lck are specialized to signal efficient cellular expansion at DN to DP transition. Moreover, although substitution of the Lck catalytic domain with FynT sequences minimally impacts DP development, single positive thymocytes are most efficiently produced in the presence of kinases containing both the NH2-terminal and catalytic regions of Lck. These findings demonstrate that the Lck structure is uniquely adapted to mediate signals at both major transitions in thymopoiesis.

Key Words: thymus • signal transduction • cellular differentiation • protein kinases • lymphocytes

K. Lin's present address is Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143-0554. J.A. Hewitt's present address is National Institute of Allergy and Infectious Diseases, National Institutes of Health–Frederick Cancer Research and Development Center, Frederick, MD 21702.

Abbreviations used in this paper: DN, double negative; DP, double positive; Lck, p56lck; LckF, activated mutant Lck; MEK, mitogen-activated protein kinase kinase; PTK, protein tyrosine kinase; Rag, recombination activating gene; Src-PTK, Src family PTK; SH, Src homology; SP, single positive.

© 2000 The Rockefeller University Press


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