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 activation at sites of hemostatic stress. We examined the relationship between TR function and T-cell activation in the Jurkat human T-cell line and in T-cell lines with defined defects in T-cell antigen receptor (TCR) function. Stimulation with thrombin or the synthetic TR peptide SFLLRN produced intracellular Ca2+ transients in Jurkat cells. As the concentration of TR agonist was increased, peak Ca2+ mobilization increased, but influx of extracellular Ca2+ decreased. TR signaling was enhanced 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 are essential for normal TCR function. TCR cross-linking with anti-CD3 IgM desensitized TR signaling in Jurkat cells, but not in CD45-deficient cells. A proteinase-activated receptor (PAR-2)-specific agonist peptide, SLIGKV, produced small Ca2+ transients in both MEG-01 human megakaryocytic cells and Jurkat cells, but was less potent than the TR-specific agonist TFRIFD in both cell types. Like TR signaling, PAR-2 signaling was enhanced in TCR-negative or lck-deficient Jurkat clones. These findings provide evidence for functional cross-talk between proteolytically activated receptors and the TCR.
Joyce
D E
DE
Veterans Affairs Medical Center, Iowa City, IA, USA.
Chen
Y
Y
Erger
R A
RA
Koretzky
G A
GA
Lentz
S R
SR
D006801:Humans; D019169:Jurkat Cells; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell; D018179:Receptors, Thrombin; D013917:Thrombin