ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor signaling, is controlled by a regulatory segment that includes a tandem SH2 unit responsible for binding to immunoreceptor tyrosine-based activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70 reveals that the inactive kinase domain adopts a conformation similar to that of cyclin-dependent kinases and S...

Syk and Zap-70 are related protein-tyrosine kinases implicated in antigen and Fc receptor signaling. While Zap-70 is restricted to T-cells and natural killer cells, Syk accumulates in B-cells, mast cells, platelets, and immature T-cells. In addition, we found that an isoform of Syk (SykB), which carries a 23-amino acid deletion in the "linker" region, is prominently expressed in bone marrow. To...

Chemokines regulate the homeostatic trafficking of lymphocytes and lymphocyte influx into sites of injury and inflammation. The signaling pathways by which chemokine receptors regulate lymphocyte migration remain incompletely characterized. We demonstrate that Jurkat T cells lacking the ZAP-70 tyrosine kinase exhibit reduced migration in response to the CXCR4 ligand CXCL12 when compared with wi...

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 p...

Expression of ZAP-70 is an important negative prognostic factor in chronic lymphocytic leukemia (CLL). This protein tyrosine kinase is a key mediator of T-cell receptor (TCR) signaling and is structurally homologous to Syk, which plays an analogous role in B-cell receptor (BCR) signaling. Recent studies indicate that ZAP-70 may participate in BCR signaling as well, but the mechanism of action i...

PURPOSE Immunoglobulin heavy chain variable-region (VH) gene mutation status and zeta-associated protein 70 (ZAP-70) expression are correlated in chronic lymphocytic leukemia (CLL), but their concordance is variable. The goal of this study was to elucidate additional factors potentially characterizing their discordance. PATIENTS AND METHODS We evaluated ZAP-70 expression by flow cytometry, VH...

The TCR zeta-chain-associated protein of 70 kDA (ZAP-70) and Syk tyrosine kinases play critical roles in regulating TCR-mediated signal transduction. They not only share some overlapped functions but also may play unique roles in regulating the function and development of T cells. However, it is not known whether they have different effects on the activation and activation-induced cell death of...

Stimulation of the CD3/TCR results within minutes in an increase in T cell adhesion mediated by beta(1) integrins. The biochemical pathways that control CD3-mediated increases in beta(1) integrin-mediated adhesion remain poorly characterized. In this study, the role of the tyrosine kinase ZAP-70 in the regulation of beta(1) integrin activity by the CD3/TCR was investigated. CD3 stimulation did ...