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*
Howard Hughes Medical Institute, Department of Medicine,
Department of Dermatology, and
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; and
§
Division of Rheumatology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030
The Syk/ZAP-70 family of protein tyrosine kinases is indispensable
for normal lymphoid development. Syk is necessary for the development
of B cells and epithelial 
T cells, whereas ZAP-70 is essential
for the normal development of T cells and TCR signaling. In this study,
we show that although development of the 
ß lineage was arrested in
the thymus, CD3-positive T cells, primarily of the lineage, were
present in the lymph nodes of mice lacking ZAP-70. Moreover, in the
absence of ZAP-70, dendritic epidermal T cells were fewer in number and
of abnormal morphology, and intestinal intraepithelial lymphocytes,
normally containing a large proportion of T cells, were markedly
reduced. These data suggest that T cells show a variable
dependence upon ZAP-70 for their development. Biochemical analyses of
thymocytes revealed a lack of basal 
-chain tyrosine phosphorylation.
However, several other substrates were inducibly tyrosine
phosphorylated following TCR stimulation. Thus, TCR-mediated signaling
in ZAP-70-deficient thymocytes is only partially impaired. These
studies suggest that Syk compensates only partially for the loss of
ZAP-70, and that there is an absolute requirement of ZAP-70 for ß
T cells and epithelial T cells, but not for some T cells
in peripheral lymphoid tissues.
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