Gene Symbol: Zap70
Description: zeta chain of T cell receptor associated protein kinase 70
Alias: Srk, tyrosine-protein kinase ZAP-70, syk-related protein tyrosine kinase, zeta-chain (TCR) associated protein kinase 70
Species: rat
Products:     Zap70

Top Publications

  1. Wiest D, Ashe J, Howcroft T, Lee H, Kemper D, Negishi I, et al. A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity. 1997;6:663-71 pubmed
    ..The developmental arrest is due to the inability of CD4+ CD8+ thymocytes to propagate TCR signals in the absence of ZAP-70 kinase activity despite tyrosine phosphorylation of TCR-associated ZAP-70 molecules. ..
  2. Lesourne R, Zvezdova E, Song K, El Khoury D, Uehara S, Barr V, et al. Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function. J Immunol. 2012;189:1154-61 pubmed publisher
    ..These results suggest that conserved molecular features of the Themis1 and Themis2 proteins are important for their biological activity and predict that Themis1 and Themis2 may perform similar functions in T and B cells, respectively. ..
  3. Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger T, et al. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004;20:37-46 pubmed
    ..Therefore, Sts-1 and Sts-2 are critical regulators of the signaling pathways that regulate T cell activation. ..
  4. Cheng A, Negishi I, Anderson S, Chan A, Bolen J, Loh D, et al. The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. Proc Natl Acad Sci U S A. 1997;94:9797-801 pubmed
    ..These data suggest that the ZAP-70 and Syk tyrosine kinases have crucial but overlapping functions in signaling from the pre-TCR and hence in early thymocyte development. ..
  5. Gauen L, Zhu Y, Letourneur F, Hu Q, Bolen J, Matis L, et al. Interactions of p59fyn and ZAP-70 with T-cell receptor activation motifs: defining the nature of a signalling motif. Mol Cell Biol. 1994;14:3729-41 pubmed
    ..We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59fyn, phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity. ..
  6. Chan A, Iwashima M, Turck C, Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992;71:649-62 pubmed
    ..Moreover, tyrosine phosphorylation and association of ZAP-70 with zeta require the presence of src family PTKs and provide a potential mechanism by which the src family PTKs and ZAP-70 may interact to mediate TCR signal transduction. ..
  7. Hatterer E, Benon A, Chounlamountri N, Watrin C, Angibaud J, Jouanneau E, et al. Syk kinase is phosphorylated in specific areas of the developing nervous system. Neurosci Res. 2011;70:172-82 pubmed publisher
    ..Therefore, Syk appears to be a serious candidate in connecting immunoreceptors to downstream adaptor/effector molecules in neurons. ..
  8. Negishi I, Motoyama N, Nakayama K, Senju S, Hatakeyama S, Zhang Q, et al. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature. 1995;376:435-8 pubmed
    ..Natural killer cell function was intact in the absence of ZAP-70. These data suggest that ZAP-70 is a central signalling molecule during thymic selection for CD4 and CD8 lineage. ..
  9. Latour S, Chow L, Veillette A. Differential intrinsic enzymatic activity of Syk and Zap-70 protein-tyrosine kinases. J Biol Chem. 1996;271:22782-90 pubmed
    ..Taken together, these data demonstrated that the intrinsic enzymatic activity of Syk and SykB is superior to that of Zap-70 and that such a distinction relates to structural variations in the catalytic domain. ..

More Information


  1. Takaki S, Watts J, Forbush K, Nguyen N, Hayashi J, Alberola Ila J, et al. Characterization of Lnk. An adaptor protein expressed in lymphocytes. J Biol Chem. 1997;272:14562-70 pubmed
    ..Together these studies suggest that Lnk participates in signaling from receptors other than antigen receptors in lymphocytes. ..
  2. Chan A, van Oers N, Tran A, Turka L, Law C, Ryan J, et al. Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 1994;152:4758-66 pubmed
    ..Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development. ..
  3. Arpaia E, Shahar M, Dadi H, Cohen A, Roifman C. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell. 1994;76:947-58 pubmed
    ..Thus, Zap-70 kinase appears to be indispensable for the development of CD8 single-positive T cells as well as for signal transduction and function of single-positive CD4 T cells. ..
  4. Hatakeyama S, Jensen J, Weissman A. Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J Biol Chem. 1997;272:15085-92 pubmed
    ..Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s. ..
  5. Morford L, Forrest K, Logan B, Overstreet L, Goebel J, Brooks W, et al. Calpain II colocalizes with detergent-insoluble rafts on human and Jurkat T-cells. Biochem Biophys Res Commun. 2002;295:540-6 pubmed
    ..Hence, we demonstrate that the positioning of calpain II within T-cell lipid rafts strategically places it in close proximity to known calpain substrates that are cleaved during Ag-specific T-cell signaling and immune synapse formation. ..
  6. Alonso A, Rahmouni S, Williams S, van Stipdonk M, Jaroszewski L, Godzik A, et al. Tyrosine phosphorylation of VHR phosphatase by ZAP-70. Nat Immunol. 2003;4:44-8 pubmed
    ..These results suggest that VHR is a target for ZAP-70 and tempers activation of the Erk2 pathway in a ZAP-70-controlled manner. ..
  7. Luo H, Yu G, Tremblay J, Wu J. EphB6-null mutation results in compromised T cell function. J Clin Invest. 2004;114:1762-73 pubmed
    ..Further downstream, in the absence of EphB6, ZAP-70 activation, LAT phosphorylation, the association of PLCgamma1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function. ..
  8. Gu Y, Chae H, Siefring J, Jasti A, Hildeman D, Williams D. RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development. Nat Immunol. 2006;7:1182-90 pubmed
    ..RhoH deficiency resulted in defective CD3zeta phosphorylation, impaired translocation of the signaling molecule Zap70 to the immunological synapse and reduced activation of Zap70-mediated signaling in thymic and peripheral T cells...