This Article
Right arrow Full Text
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 Zhao, Q.
Right arrow Articles by Weiss, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Q.
Right arrow Articles by Weiss, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 1999, p. 948-956, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interdomain B in ZAP-70 Regulates but Is Not Required for ZAP-70 Signaling Function in Lymphocytes

Qihong Zhao,1 Brandi L. Williams,2 Robert T. Abraham,2 and Arthur Weiss1,*

Department of Medicine, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143-0795;1 and Department of Immunology, Mayo Clinic, Rochester, Minnesota 559052

Received 7 July 1998/Returned for modification 19 August 1998/Accepted 19 October 1998

The protein tyrosine kinase ZAP-70 plays an important role in T-cell activation and development. After T-cell receptor stimulation, ZAP-70 associates with the receptor and is phosphorylated on many tyrosines, including Y292, Y315, and Y319 within interdomain B. Previously, we demonstrated that Y292 negatively regulates ZAP-70 function and that Y315 positively regulates ZAP-70 function by interacting with Vav. Recent studies have suggested that Y319 also positively regulate ZAP-70 function. Paradoxically, removal of interdomain B (to create the construct designated Delta ), containing the Y292, Y315, and Y319 sites, did not eliminate the ability of ZAP-70 to induce multiple gene reporters in Syk-deficient DT-40 B cells and ZAP-70/Syk-deficient Jurkat cells. Here we show that Delta  still utilizes the same pathways as wild-type ZAP-70 to mediate NF-AT induction. This is manifested by the ability of Delta  to restore induction of calcium fluxes and mitogen-activated protein kinase activation and by the ability of dominant negative Ras and FK506 to block the induction of NF-AT activity mediated by Delta . Biochemically we show that the stimulated tyrosine phosphorylation of Vav, Shc, and ZAP-70 itself is diminished, whereas that of Slp-76 is increased in cells reconstituted with Delta . Deletion of interdomain B did not affect the ability of ZAP-70 to bind to the receptor. The in vitro kinase activity of ZAP-70 lacking interdomain B was markedly reduced, but the kinase activity was still required for the protein's in vivo activity. Based on these data, we concluded that interdomain B regulates but is not required for ZAP-70 signaling function leading to cellular responses.

* Corresponding author. Mailing address: Box 0795, Third and Parnassus Ave., San Francisco, CA 94143. Phone: (415) 476-1291. Fax: (415) 502-5081. E-mail: aweiss{at}itsa.ucsf.edu.

Molecular and Cellular Biology, January 1999, p. 948-956, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Weiss, A. (2009). TCR Signal Transduction: Opening the Black Box. J. Immunol. 183: 4821-4827 [Full Text]  
  • Zhang, Y., Oh, H., Burton, R. A., Burgner, J. W., Geahlen, R. L., Post, C. B. (2008). Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling. Proc. Natl. Acad. Sci. USA 105: 11760-11765 [Abstract] [Full Text]  
  • Levin, S. E., Zhang, C., Kadlecek, T. A., Shokat, K. M., Weiss, A. (2008). Inhibition of ZAP-70 Kinase Activity via an Analog-sensitive Allele Blocks T Cell Receptor and CD28 Superagonist Signaling. J. Biol. Chem. 283: 15419-15430 [Abstract] [Full Text]  
  • Chandok, M. R., Okoye, F. I., Ndejembi, M. P., Farber, D. L. (2007). A Biochemical Signature for Rapid Recall of Memory CD4 T Cells. J. Immunol. 179: 3689-3698 [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]  
  • Brdicka, T., Kadlecek, T. A., Roose, J. P., Pastuszak, A. W., Weiss, A. (2005). Intramolecular Regulatory Switch in ZAP-70: Analogy with Receptor Tyrosine Kinases. Mol. Cell. Biol. 25: 4924-4933 [Abstract] [Full Text]  
  • Steinberg, M., Adjali, O., Swainson, L., Merida, P., Bartolo, V. D., Pelletier, L., Taylor, N., Noraz, N. (2004). T-cell receptor-induced phosphorylation of the {zeta} chain is efficiently promoted by ZAP-70 but not Syk. Blood 104: 760-767 [Abstract] [Full Text]  
  • Goda, S., Quale, A. C., Woods, M. L., Felthauser, A., Shimizu, Y. (2004). Control of TCR-Mediated Activation of {beta}1 Integrins by the ZAP-70 Tyrosine Kinase Interdomain B Region and the Linker for Activation of T Cells Adapter Protein. J. Immunol. 172: 5379-5387 [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]  
  • 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]  
  • 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]  
  • Bustelo, X. R. (2000). Regulatory and Signaling Properties of the Vav Family. Mol. Cell. Biol. 20: 1461-1477 [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»