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J. Biol. Chem. 276 (37): 34722-34727

© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

Transient Tyrosine Phosphorylation of Human Ryanodine Receptor upon T Cell Stimulation*

Andreas H. GuseDagger §, Alexander Y. Tsygankov, Karin WeberDagger , and Georg W. MayrDagger

From the Dagger  Division of Cellular Signal Transduction, Institute for Medical Biochemistry and Molecular Biology, University of Hamburg, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany and the  Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

The ryanodine receptor of Jurkat T lymphocytes was phosphorylated on tyrosine residues upon stimulation of the cells via the T cell receptor/CD3 complex. The tyrosine phosphorylation was transient, reaching a maximum at 2 min, and rapidly declined thereafter. In co-immunoprecipitates of the ryanodine receptor, the tyrosine kinases p56lck and p59fyn were detected. However, only p59fyn associated with the ryanodine receptor in a stimulation-dependent fashion. Both tyrosine kinases, recombinantly expressed as glutathione S-transferase (GST) fusion proteins, phosphorylated the immunoprecipitated ryanodine receptor in vitro. In permeabilized Jurkat T cells, GST-p59fyn, but not GST-p56lck, GST-Grb2, or GST alone, significantly and concentration-dependently enhanced Ca2+ release by cyclic ADP-ribose. The tyrosine kinase inhibitor PP2 specifically blocked the effect of GST-p59fyn. This indicates that intracellular Ca2+ release via ryanodine receptors may be modulated by tyrosine phosphorylation during T cell activation.

* This work was supported by Deutsche Forschungsgemeinschaft Grants Gu 360/2-4 and Gu 360/2-5 (to A. H. G. and G. W. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed. Tel.: 49-40-42803-2828; Fax: 49-40-42803-9880; E-mail:

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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