Transient tyrosine phosphorylation of human ryanodine receptor upon T cell stimulation.

J Biol Chem

Division of Cellular Signal Transduction, Institute for Medical Biochemistry and Molecular Biology, University of Hamburg, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.

Published: September 2001

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 p56(lck) and p59(fyn) were detected. However, only p59(fyn) 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-p59(fyn), but not GST-p56(lck), GST-Grb2, or GST alone, significantly and concentration-dependently enhanced Ca(2+) release by cyclic ADP-ribose. The tyrosine kinase inhibitor PP2 specifically blocked the effect of GST-p59(fyn). This indicates that intracellular Ca(2+) release via ryanodine receptors may be modulated by tyrosine phosphorylation during T cell activation.

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http://dx.doi.org/10.1074/jbc.M100715200DOI Listing

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