FUNCTIONAL INTERACTIONS BETWEEN THE THROMBIN RECEPTOR AND THE T-CELL ANTIGEN RECEPTOR IN HUMAN T-CELL LINES

The proteolytically activated thrombin receptor (TR) is expressed by T lymphocytes, which suggests that thrombin may modulate T-cell activat ion at sites of hemostatic stress, We examined the relationship betwee n TR function and T-cell activation in the Jurkat human T-cell line an d in T-cell lines with defined defects in T-cell antigen receptor (TCR ) function, Stimulation with thrombin or the synthetic TR peptide SFLL RN produced intracellular Ca2+ transients in Jurkat cells. As the conc entration of TR agonist was increased, peak Ca2+ mobilization increase d, but influx of extracellular Ca2+ decreased. TR signaling was enhanc ed in a TCR-negative Jurkat line and in T-cell lines deficient in the tyrosine kinase lck or the tyrosine phosphatase CD45, both of which ar e essential for normal TCR function. TCR cross-linking with anti-CD3 I gM desensitized TR signaling in Jurkat cells, but not in CD45-deficien t cells. A proteinase-activated receptor (PAR-2)-specific agonist pept ide, SLIGKV, produced small Ca2+ transients in both MEG-01 human megak aryocytic cells and Jurkat cells, but was less potent than the TR-spec ific agonist TFRIFD in both cell types. Like TR signaling, PAR2 signal ing was enhanced in TCR-negative or lck-deficient Jurkat clones. These findings provide evidence for functional cross-talk between proteolyt ically activated receptors and the TCR. (C) 1997 by The American Socie ty of Hematology.