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The structure, regulation, and function of ZAP-70

Byron B Au-Yeung1, Sebastian Deindl, Lih-Yun Hsu

  • 1Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143-0795, USA.

Immunological Reviews
|March 18, 2009
PubMed

The tyrosine ZAP-70 (zeta-associated protein of 70 kDa) kinase plays a critical role in activating many downstream signal transduction pathways in T cells following T-cell receptor (TCR) engagement. The importance of ZAP-70 is evidenced by the severe combined immunodeficiency that occurs in ZAP-70-deficient mice and humans. In this review, we describe recent analyses of the ZAP-70 crystal structure, revealing a complex regulatory mechanism of ZAP-70 activity, the differential requirements for ZAP-70 and spleen tyrosine kinase (SyK) in early T-cell development, as well as the role of ZAP-70 in chronic lymphocytic leukemia and autoimmunity. Thus, the critical importance of ZAP-70 in TCR signaling and its predominantly T-cell-restricted expression pattern make ZAP-70 an attractive drug target for the inhibition of pathological T-cell responses in disease.

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