User:BennieDai01/ZAP70

= Zap-70 = Zeta-chain-associated protein kinase-70 (ZAP-70) is a tyrosine kinase that is expressed in lymphocytes (NK cells, T Cells, and a subset of B cells). It is important in the signal transduction pathways of these lymphocytes, and it is related to lymphocyte activation and development.

Zap-70 and T cell activation
The T cell receptor has no innate enzymatic activity. Due to this, T cell receptors rely on signalling molecules to transduce a signal from the cell membrane. ZAP-70 is a cytoplasmic tyrosine kinase that initiates a signal pathway downstream of the T cell receptor after binding from an MHC molecule of an antigen presenting cell. Immunoreceptor tyrosine-based activation motifs (ITAMS) contain two tyrosines that act as substrates for the Src family kinase. When the T cell receptor binds to MHC, the ITAMs will interact with the protein Lck, another protein in the signalling pathway. Lck-mediated phosphorylation of the ITAM tyrosines signals the recruitment of ZAP-70, which continues the signaling pathway.

Zap-70 and Chronic Lymphocytic Leukemia (CLL)
Due to its role in T cell and NK cell signaling, ZAP-70 has been associated with diseases affecting lymphocytes. ZAP-70 has been associated with chronic lymphocytic leukemia (CLL). ZAP-70 expression is a significant indicator of the overall survival and event free survival of lymphocytes, due to their role in T cell and NK signalling and development. In individuals with CLL, higher levels of ZAP-70 is associated with a higher amount of lymphocytes activated, further promoting advancement of CLL. Not only is ZAP-70 associated with T cell and NK cell activation, but its expression is also associated with B cell malignancies in CLL. Higher expression of ZAP-70 in B cell malignancies is correlated to a higher amount of cellular signals when the BCR is activated. Overall, due to ZAP-70’s role in lymphocyte activation, it is clear to see an association between high levels of ZAP-70 and CLL advancement.