Phospho-ZAP-70 (Y319) Polyclonal Antibody, 100 µg, (ATB-P0276)

Description

Background:

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).

Product datasheet:

References:

1. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain.
   Chan A.C., Iwashima M., Turck C.W., Weiss A.
   Cell 71:649-662(1992) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CD3Z, TISSUE SPECIFICITY, PHOSPHORYLATION.
2. Identification of a novel isoform of ZAP-70, truncated ZAP kinase.
   Kuroyama H., Ikeda T., Kasai M., Yamasaki S., Tatsumi M., Utsuyama M., Saito T., Hirokawa K.
   Biochem. Biophys. Res. Commun. 315:935-941(2004) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Leukocyte.
3. Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
   , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
   Nature 434:724-731(2005) [PubMed] [Europe PMC]

   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
   The MGC Project Team
   Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Blood and Brain.
5. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase.
   Arpaia E., Shahar M., Dadi H., Cohen A., Roifman C.M.
   Cell 76:947-958(1994) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 521-547, VARIANT STCD LEU-GLU-GLN-541 INS, FUNCTION. Tissue: Lymphoid tissue.
6. ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity.
   Isakov N., Wange R.L., Burgess W.H., Watts J.D., Aebersold R., Samelson L.E.
   J. Exp. Med. 181:375-380(1995) [PubMed] [Europe PMC] Cited for: CHARACTERIZATION OF TAM-BINDING.
7. Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.
   Chan A.C., Dalton M., Johnson R., Kong G.H., Wang T., Thoma R., Kurosaki T.
   EMBO J. 14:2499-2508(1995) [PubMed] [Europe PMC] Cited for: MUTAGENESIS OF TYR-492 AND TYR-493.
8. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.
   Bubeck Wardenburg J., Fu C., Jackman J.K., Flotow H., Wilkinson S.E., Williams D.H., Johnson R., Kong G., Chan A.C., Findell P.R.
   J. Biol. Chem. 271:19641-19644(1996) [PubMed] [Europe PMC] Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
9. Enhancement of lymphocyte responsiveness by a gain-of-function mutation of ZAP-70.
   Zhao Q., Weiss A.
   Mol. Cell. Biol. 16:6765-6774(1996) [PubMed] [Europe PMC] Cited for: PHOSPHORYLATION AT TYR-292, MUTAGENESIS OF TYR-292.
10. The Vav binding site (Y315) in ZAP-70 is critical for antigen receptor-mediated signal transduction.
    Wu J., Zhao Q., Kurosaki T., Weiss A.
    J. Exp. Med. 185:1877-1882(1997) [PubMed] [Europe PMC] Cited for: INTERACTION WITH VAV1, MUTAGENESIS OF TYR-315.