ZAP70 tyrosinekinase

ZAP-70 is the acronym for "zeta-chain-associated protein kinase 70". ZAP-70 is a cytosolic protein tyrosine kinase, with a molecular weight of 70 kDa, phyiolopgically expressed near the surface membrane of lymphocytes (T cells, natural killer cells, and a subset of B cells). ZAP70 tyrosine kinase is encoded by the ZAP70 gene. The protein tyrosine kinase is primarily involved in antigen binding to the T cell receptor (TCR) and plays a critical role in T cell signaling.

The T cell receptor (TCR) has no enzymatic activity of its own. For this reason, T cell receptors rely on signaling molecules to relay a signal from the cell membrane. ZAP-70 is an important cytoplasmic tyrosine kinase that opens a signaling pathway downstream of an activated T cell receptor.

Due to its role in lymphocyte signaling, ZAP-70 has been associated with several diseases affecting lymphocytes (see also ZAP-70 deficiency). ZAP-70 expression is an important indicator of lymphocyte survival and has been particularly associated with chronic lymphocytic leukemia (CLL). In individuals with CLL, higher ZAP-70 levels are associated with higher numbers of activated malignant B cells. Increased expression of ZAP 70 in malignant B cells correlates with increased association between malignant B cells and the immune environment, suggesting a complex role for ZAP-70 in B cell signaling.

Based on the relationship between ZAP-70 and B-cell malignancies, ZAP-70 can be used as a prognostic biomarker to identify different forms of CLL (Chen J et al 2020).

In systemic lupus erythematosus, the Zap-70 receptor pathway is absent and Syk takes its place (Vásquez A et al. 2019).

Deficiency of ZAP-70 leads to an autosomal recessive form of immunodeficiency called combined immunodeficiency (ZAP-70 deficiency).

Patients suffering from combined immunodeficiency have normal lymphocyte counts but low levels of T helper cells and cytotoxic T cells.

Patients have also been found to have irregular lymphocyte proliferation. These effects suggest that deficiency of ZAP-70 leads to decreased T cell activation and subsequent signal transduction.

1. Au-Yeung BB et al (2018) ZAP-70 in Signaling, Biology, and Disease. Annual Review of Immunology 36: 127-156.
2. Chen J et al (2020) ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies. Frontiers in Oncology 10: 595832.
3. Liu Y et al. (2018) ZAP-70 in chronic lymphocytic leukemia: A meta-analysis. Clinica Chimica Acta ; International Journal of Clinical Chemistry 483: 82-88.
4. Lindholm CK et al.(2002) Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells. European Journal of Biochemistry 269: 3279-88.

5. Vásquez A et al. (2019) Altered recruitment of Lyn, Syk and ZAP-70 into lipid rafts of activated B cells in Systemic Lupus Erythematosus. Cell Signal 58:9-19.

6. Wang H et al (2010) ZAP-70: an essential kinase in T-cell signaling. Cold Spring Harbor Perspectives in Biology 2: a002279.