ZAP-70 (Zeta-associated protein of 70-kD)

A cytoplasmic tyrosine kinase essential for signaling molecule for T-lymphocytes and natural killer cells.

Anomalously expressed in CLL cells with unmutated IgVh genes and may enhance the signaling process when B-cell receptor is engaged.

Associated with CD3 receptor complex of the lymphocytes ad the Syk family of tyrosine kinases.

Plays a role in signaling, activation and phosphorylation of downstream targets.

T cells contain more ZAP-70 than B cells.

Intracellular ZAP-70 content correlates with IgVh mutation.

Expression in CLL associated with a more rapid progression and shorter survival.

Can be expressed in other hematologic neoplasms aside from CLL, such associated precursor B cell ALL, mantle cell lymphoma, diffuse large B cell lymphoma and Burkitt’s lymphoma.

ZAP-70 (Zeta-chain-associated protein kinase 70).

A protein normally expressed near the surface membrane of T cells and natural killer cells.

It is part of the T cell receptor.

It plays a critical role in T-cell signaling.

Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family.

Gene location is on Chromosome 2

ZAP-70 in B cells is used as a prognostic marker to identify the prognosis of different forms of chronic lymphocytic leukemia (CLL).

CLL that is positive for the marker ZAP-70 has an average survival of 8 years.

CLL that is negative for ZAP-70 has an average survival of more than 25 years, so that patients, especially older ones, with slowly progressing disease can be reassured and may not need any treatment in their lifetimes.

In systemic lupus erythematosus, the Zap-70 receptor pathway is missing and Syk takes its place.

ZAP70 deficiency results in a form of immune deficiency.

The TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase Lck.

Lck phosphorylates the intracellular portions of the CD3 creates a docking site for ZAP-70.

The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds.

T cell activation by ZAP-70 is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines.

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