ZAP70 (Chronic Lymphocytic Leukemia Marker) Antibody
Mouse Monoclonal Antibody [Clone ZAP70/528 + 2F3.2 ]
|Application ||IHC, IF, FC|
|Other Accession||7535, 234569|
|Isotype||Mouse / IgG's|
|Clone Names||ZAP70/528 + 2F3.2|
|Other Names||Tyrosine-protein kinase ZAP-70, 188.8.131.52, 70 kDa zeta-chain associated protein, Syk-related tyrosine kinase, ZAP70, SRK|
|Storage||Store at 2 to 8°C.Antibody is stable for 24 months.|
|Precautions||ZAP70 (Chronic Lymphocytic Leukemia Marker) Antibody is for research use only and not for use in diagnostic or therapeutic procedures.|
|Function||Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).|
|Cellular Location||Cytoplasm. Cell membrane; Peripheral membrane protein. Note=In quiescent T-lymphocytes, it is cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD247/CD3Z. Colocalizes together with RHOH in the immunological synapse. RHOH is required for its proper localization to the cell membrane and cytoskeleton fractions in the thymocytes (By similarity).|
|Tissue Location||Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells|
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ZAP70 is a 70kDa protein tyrosine kinase found in T-cells and natural killer cells.ĀControl of this protein translation is via the IgVH gene. ZAP70 protein is expressed in leukemic cells of approximately 25% of chronic lymphocytic leukemia (CLL) cases as well.ĀAnti-ZAP70 expression is an excellent surrogate marker for the distinction between the Ig-mutated (anti-ZAP70 negative) and Ig-unmutated (anti-ZAP70 positive) CLL subtypes and can identify patient groups with divergent clinical courses. The anti-ZAP70 positive Ig-unmutated CLL cases have been shown to have a poorer prognosis.
Iwashima M, Irving BA, van Oers NSC, Chan AC, Weiss A. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science 1994;263:1136-9
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