This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kong, G.
Right arrow Articles by Chan, A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kong, G.
Right arrow Articles by Chan, A. C.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Sep 1996, 5026-5035, Vol 16, No. 9
Copyright © 1996, American Society for Microbiology

Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function

G Kong, M Dalton, JB Wardenburg, D Straus, T Kurosaki and AC Chan
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Biochemical and genetic evidence has implicated two families of protein tyrosine kinases (PTKs), the Src- and Syk-PTKs, in T- and B-cell antigen receptor signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Three tyrosine residues, Tyr-292, -492, and -493, have been identified as sites of phosphorylation following T-cell antigen receptor engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk-DT40 cells), we provide biochemical and functional evidence that heterologous trans- phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated activation of both the calcium and ras pathways. In contrast, cells expressing mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and inactivation of antigen receptor signaling.


This article has been cited by other articles:

  • Maier, L. M., Anderson, D. E., De Jager, P. L., Wicker, L. S., Hafler, D. A. (2007). Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proc. Natl. Acad. Sci. USA 104: 18607-18612 [Abstract] [Full Text]  
  • Roberts, J. L., Lauritsen, J. P. H., Cooney, M., Parrott, R. E., Sajaroff, E. O., Win, C. M., Keller, M. D., Carpenter, J. H., Carabana, J., Krangel, M. S., Sarzotti, M., Zhong, X.-P., Wiest, D. L., Buckley, R. H. (2007). T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3{zeta} subunit of the T-cell antigen receptor complex. Blood 109: 3198-3206 [Abstract] [Full Text]  
  • Espagnolle, N., Depoil, D., Zaru, R., Demeur, C., Champagne, E., Guiraud, M., Valitutti, S. (2007). CD2 and TCR synergize for the activation of phospholipase C{gamma}1/calcium pathway at the immunological synapse. Int Immunol 19: 239-248 [Abstract] [Full Text]  
  • Kim, J.-E., White, F. M. (2006). Quantitative analysis of phosphotyrosine signaling networks triggered by CD3 and CD28 costimulation in jurkat cells.. J. Immunol. 176: 2833-2843 [Abstract] [Full Text]  
  • Crespo, M., Villamor, N., Gine, E., Muntanola, A., Colomer, D., Marafioti, T., Jones, M., Camos, M., Campo, E., Montserrat, E., Bosch, F. (2006). ZAP-70 Expression in Normal Pro/Pre B Cells, Mature B Cells, and in B-Cell Acute Lymphoblastic Leukemia. Clin. Cancer Res. 12: 726-734 [Abstract] [Full Text]  
  • Gelkop, S., Gish, G. D., Babichev, Y., Pawson, T., Isakov, N. (2005). T Cell Activation-Induced CrkII Binding to the Zap70 Protein Tyrosine Kinase Is Mediated by Lck-Dependent Phosphorylation of Zap70 Tyrosine 315. J. Immunol. 175: 8123-8132 [Abstract] [Full Text]  
  • Zhong, L., Wu, C.-H., Lee, W.-H., Liu, C.-P. (2004). {zeta}-Associated Protein of 70 kDa (ZAP-70), but Not Syk, Tyrosine Kinase Can Mediate Apoptosis of T Cells through the Fas/Fas Ligand, Caspase-8 and Caspase-3 Pathways. J. Immunol. 172: 1472-1482 [Abstract] [Full Text]  
  • Thien, C. B.F., Scaife, R. M., Papadimitriou, J. M., Murphy, M. A., Bowtell, D. D.L., Langdon, W. Y. (2003). A Mouse with a Loss-of-function Mutation in the c-Cbl TKB Domain Shows Perturbed Thymocyte Signaling without Enhancing the Activity of the ZAP-70 Tyrosine Kinase. JEM 197: 503-513 [Abstract] [Full Text]  
  • Zhang, J., Berenstein, E., Siraganian, R. P. (2002). Phosphorylation of Tyr342 in the Linker Region of Syk Is Critical for Fc{varepsilon}RI Signaling in Mast Cells. Mol. Cell. Biol. 22: 8144-8154 [Abstract] [Full Text]  
  • Rao, N., Dodge, I., Band, H. (2002). The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system. J. Leukoc. Biol. 71: 753-763 [Abstract] [Full Text]  
  • Veri, M.-C., DeBell, K. E., Seminario, M.-C., DiBaldassarre, A., Reischl, I., Rawat, R., Graham, L., Noviello, C., Rellahan, B. L., Miscia, S., Wange, R. L., Bonvini, E. (2001). Membrane Raft-Dependent Regulation of Phospholipase C{gamma}-1 Activation in T Lymphocytes. Mol. Cell. Biol. 21: 6939-6950 [Abstract] [Full Text]  
  • Magnan, A., Di Bartolo, V., Mura, A.-M., Boyer, C., Richelme, M., Lin, Y.-L., Roure, A., Gillet, A., Arrieumerlou, C., Acuto, O., Malissen, B., Malissen, M. (2001). T Cell Development and T Cell Responses in Mice with Mutations Affecting Tyrosines 292 or 315 of the Zap-70 Protein Tyrosine Kinase. JEM 194: 491-506 [Abstract] [Full Text]  
  • Gong, Q., Jin, X., Akk, A. M., Foger, N., White, M., Gong, G., Wardenburg, J. B., Chan, A. C. (2001). Requirement for Tyrosine Residues 315 and 319 within {zeta} Chain-Associated Protein 70 for T Cell Development. JEM 194: 507-518 [Abstract] [Full Text]  
  • Rao, N., Lupher, M. L. Jr., Ota, S., Reedquist, K. A., Druker, B. J., Band, H. (2000). The Linker Phosphorylation Site Tyr292 Mediates the Negative Regulatory Effect of Cbl on ZAP-70 in T Cells. J. Immunol. 164: 4616-4626 [Abstract] [Full Text]  
  • Ciccarelli, F. D., Acciarito, A., Alberti, S. (2000). Large and diverse numbers of human diseases with HIKE mutations. Hum Mol Genet 9: 1001-1007 [Abstract] [Full Text]  
  • Bouhdoud, L., Villain, P., Merzouki, A., Arella, M., Couture, C. (2000). T-Cell Receptor-Mediated Anergy of a Human Immunodeficiency Virus (HIV) gp120-Specific CD4+ Cytotoxic T-Cell Clone, Induced by a Natural HIV Type 1 Variant Peptide. J. Virol. 74: 2121-2130 [Abstract] [Full Text]  
  • Yasuda, T., Maeda, A., Kurosaki, M., Tezuka, T., Hironaka, K., Yamamoto, T., Kurosaki, T. (2000). Cbl Suppresses B Cell Receptor-Mediated Phospholipase C (Plc)-{gamma}2 Activation by Regulating B Cell Linker Protein-Plc-{gamma}2 Binding. JEM 191: 641-650 [Abstract] [Full Text]  
  • Denny, M. F., Patai, B., Straus, D. B. (2000). Differential T-Cell Antigen Receptor Signaling Mediated by the Src Family Kinases Lck and Fyn. Mol. Cell. Biol. 20: 1426-1435 [Abstract] [Full Text]  
  • Ota, S., Hazeki, K., Rao, N., Lupher, M. L. Jr., Andoniou, C. E., Druker, B., Band, H. (2000). The RING Finger Domain of Cbl Is Essential for Negative Regulation of the Syk Tyrosine Kinase. J. Biol. Chem. 275: 414-422 [Abstract] [Full Text]  
  • Sada, K., Zhang, J., Siraganian, R. P. (2000). Point Mutation of a Tyrosine in the Linker Region of Syk Results in a Gain of Function. J. Immunol. 164: 338-344 [Abstract] [Full Text]  
  • van Leeuwen, J. E. M., Paik, P. K., Samelson, L. E. (1999). The Oncogenic 70Z Cbl Mutation Blocks the Phosphotyrosine Binding Domain-Dependent Negative Regulation of ZAP-70 by c-Cbl in Jurkat T Cells. Mol. Cell. Biol. 19: 6652-6664 [Abstract] [Full Text]  
  • Zhang, J., Siraganian, R. P. (1999). CD45 Is Essential for Fc{epsilon}RI Signaling by ZAP70, But Not Syk, in Syk-Negative Mast Cells. J. Immunol. 163: 2508-2516 [Abstract] [Full Text]  
  • Thien, C. B. F., Bowtell, D. D. L., Langdon, W. Y. (1999). Perturbed Regulation of ZAP-70 and Sustained Tyrosine Phosphorylation of LAT and SLP-76 in c-Cbl-Deficient Thymocytes. J. Immunol. 162: 7133-7139 [Abstract] [Full Text]  
  • Pelosi, M., Di Bartolo, V., Mounier, V., Mege, D., Pascussi, J.-M., Dufour, E., Blondel, A., Acuto, O. (1999). Tyrosine 319 in the Interdomain B of ZAP-70 Is a Binding Site for the Src Homology 2 Domain of Lck. J. Biol. Chem. 274: 14229-14237 [Abstract] [Full Text]  
  • Di Bartolo, V., Mege, D., Germain, V., Pelosi, M., Dufour, E., Michel, F., Magistrelli, G., Isacchi, A., Acuto, O. (1999). Tyrosine 319, a Newly Identified Phosphorylation Site of ZAP-70, Plays a Critical Role in T Cell Antigen Receptor Signaling. J. Biol. Chem. 274: 6285-6294 [Abstract] [Full Text]  
  • Labuda, T., Gerwien, J., Odum, N., Dohlsten, M. (1999). Rapid tyrosine phosphorylation of Lck following ligation of the tumor-associated cell surface molecule A6H. Int Immunol 11: 427-433 [Abstract] [Full Text]  
  • Zhang, Z., Elly, C., Altman, A., Liu, Y.-C. (1999). Dual Regulation of T Cell Receptor-mediated Signaling by Oncogenic Cbl Mutant 70Z. J. Biol. Chem. 274: 4883-4889 [Abstract] [Full Text]  
  • Motoya, S., Kitamura, K., Matsuda, A., Maizel, A. L., Yamamoto, H., Takeda, A. (1999). Interaction between CD45-AP and Protein-tyrosine Kinases Involved in T Cell Receptor Signaling. J. Biol. Chem. 274: 1407-1414 [Abstract] [Full Text]  
  • Zhao, Q., Williams, B. L., Abraham, R. T., Weiss, A. (1999). Interdomain B in ZAP-70 Regulates but Is Not Required for ZAP-70 Signaling Function in Lymphocytes. Mol. Cell. Biol. 19: 948-956 [Abstract] [Full Text]  
  • Lupher Jr., M. L., Rao, N., Lill, N. L., Andoniou, C. E., Miyake, S., Clark, E. A., Druker, B., Band, H. (1998). Cbl-mediated Negative Regulation of the Syk Tyrosine Kinase. A CRITICAL ROLE FOR Cbl PHOSPHOTYROSINE-BINDING DOMAIN BINDING TO Syk PHOSPHOTYROSINE 323. J. Biol. Chem. 273: 35273-35281 [Abstract] [Full Text]  
  • Keshvara, L. M., Isaacson, C. C., Yankee, T. M., Sarac, R., Harrison, M. L., Geahlen, R. L. (1998). Syk- and Lyn-Dependent Phosphorylation of Syk on Multiple Tyrosines Following B Cell Activation Includes a Site That Negatively Regulates Signaling. J. Immunol. 161: 5276-5283 [Abstract] [Full Text]  
  • Sloan-Lancaster, J., Presley, J., Ellenberg, J., Yamazaki, T., Lippincott-Schwartz, J., Samelson, L. E. (1998). ZAP-70 Association with T Cell Receptor {zeta} (TCR{zeta}): Fluorescence Imaging of Dynamic Changes upon Cellular Stimulation. JCB 143: 613-624 [Abstract] [Full Text]  
  • Zhang, J., Kimura, T., Siraganian, R. P. (1998). Mutations in the Activation Loop Tyrosines of Protein Tyrosine Kinase Syk Abrogate Intracellular Signaling But Not Kinase Activity. J. Immunol. 161: 4366-4374 [Abstract] [Full Text]  
  • Soede, R. D.M., Wijnands, Y. M., Van Kouteren-Cobzaru, I., Roos, E. (1998). ZAP-70 Tyrosine Kinase Is Required for LFA-1-dependent T Cell Migration. JCB 142: 1371-1379 [Abstract] [Full Text]  
  • Pacini, S., Ulivieri, C., Di Somma, M. M., Isacchi, A., Lanfrancone, L., Pelicci, P. G., Telford, J. L., Baldari, C. T. (1998). Tyrosine 474 of ZAP-70 Is Required for Association with the Shc Adaptor and for T-cell Antigen Receptor-dependent Gene Activation. J. Biol. Chem. 273: 20487-20493 [Abstract] [Full Text]  
  • Murphy, M. A., Schnall, R. G., Venter, D. J., Barnett, L., Bertoncello, I., Thien, C. B. F., Langdon, W. Y., Bowtell, D. D. L. (1998). Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice. Mol. Cell. Biol. 18: 4872-4882 [Abstract] [Full Text]  
  • Zeitlmann, L., Knorr, T., Knoll, M., Romeo, C., Sirim, P., Kolanus, W. (1998). T Cell Activation Induced by Novel Gain-of-function Mutants of Syk and ZAP-70. J. Biol. Chem. 273: 15445-15452 [Abstract] [Full Text]  
  • Wong, J., Straus, D., Chan, A. C. (1998). Genetic Evidence of a Role for Lck in T-Cell Receptor Function Independent or Downstream of ZAP-70/Syk Protein Tyrosine Kinases. Mol. Cell. Biol. 18: 2855-2866 [Abstract] [Full Text]  
  • Griffith, C. E., Zhang, W., Wange, R. L. (1998). ZAP-70-dependent and -independent Activation of Erk in Jurkat T Cells. DIFFERENCES IN SIGNALING INDUCED BY H2O2 AND CD3 CROSS-LINKING. J. Biol. Chem. 273: 10771-10776 [Abstract] [Full Text]  
  • Williams, B. L., Schreiber, K. L., Zhang, W., Wange, R. L., Samelson, L. E., Leibson, P. J., Abraham, R. T. (1998). Genetic Evidence for Differential Coupling of Syk Family Kinases to the T-Cell Receptor: Reconstitution Studies in a ZAP-70-Deficient Jurkat T-Cell Line. Mol. Cell. Biol. 18: 1388-1399 [Abstract] [Full Text]  
  • Lupher Jr., M. L., Songyang, Z., Shoelson, S. E., Cantley, L. C., Band, H. (1997). The Cbl Phosphotyrosine-binding Domain Selects a D(N/D)XpY Motif and Binds to the Tyr292 Negative Regulatory Phosphorylation Site of ZAP-70. J. Biol. Chem. 272: 33140-33144 [Abstract] [Full Text]  
  • Zhou, Y.-J., Hanson, E. P., Chen, Y.-Q., Magnuson, K., Chen, M., Swann, P. G., Wange, R. L., Changelian, P. S., O'Shea, J. J. (1997). Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. Proc. Natl. Acad. Sci. USA 94: 13850-13855 [Abstract] [Full Text]  
  • Sloan-Lancaster, J., Zhang, W., Presley, J., Williams, B. L., Abraham, R. T., Lippincott-Schwartz, J., Samelson, L. E. (1997). Regulation of ZAP-70 Intracellular Localization: Visualization with the Green Fluorescent Protein. JEM 186: 1713-1724 [Abstract] [Full Text]  
  • Huby, R. D.J., Iwashima, M., Weiss, A., Ley, S. C. (1997). ZAP-70 Protein Tyrosine Kinase Is Constitutively Targeted to the T Cell Cortex Independently of its SH2 Domains. JCB 137: 1639-1649 [Abstract] [Full Text]  
  • Keshvara, L. M., Isaacson, C., Harrison, M. L., Geahlen, R. L. (1997). Syk Activation and Dissociation from the B-cell Antigen Receptor Is Mediated by Phosphorylation of Tyrosine 130. J. Biol. Chem. 272: 10377-10381 [Abstract] [Full Text]  
  • Zhang, J., Billingsley, M. L., Kincaid, R. L., Siraganian, R. P. (2000). Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. AN IN VIVO STUDY USING A SPECIFIC ANTI-Syk ACTIVATION LOOP PHOSPHOTYROSINE ANTIBODY. J. Biol. Chem. 275: 35442-35447 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»