Abstract
His-Phe-Tyr-Leu-Pro-Met (HFYLPM) is a synthetic peptide that stimulates Jurkat T cells resulting in intracellular calcium ([Ca2+]i) increase in a pertussis toxin (PTX)-sensitive manner. We have examined the physiological role of the peptide in T cell activity by comparative investigation of intracellular signaling pathways accompanied with HFYLPM-induced T cell chemotaxis with a well-known chemokine, stromal cell-derived factor-1 (SDF-1)-induced signalings. Wortmannin and genistein inhibited both of HFYLPM- and SDF-1-induced Jurkat T cell chemotaxis indicating that phosphoinositide-3-kinase and tyrosine kinase activity were required for the processes. However, U-73122 and BAPTA/AM preferentially blocked HFYLPM- but not SDF-1-induced T cell chemotaxis. It indicates that phospholipase C/calcium signaling is necessary for only chemotaxis by HFYLPM. One of the well-known cellular molecules involving chemotaxis, extracellular signal-regulated protein kinase (ERK), was activated by SDF-1 but not by HFYLPM ruling out a possible role of ERK on the peptide-mediated chemotaxis. These results indicate that the synthetic peptide, HFYLPM, stimulates T cell chemotaxis showing unique signaling and provide a useful tool for the study of T cell activation mechanism.
Highlights
T cells have a central role in the regulation of immune responses in host immunity (Goetzl et al 1992; Lee et al 1999)
The result indicates that the synthetic peptide, HFYLPM, stimulates Jurkat T cells leading to [Ca2+]i increase, and pertussis toxin (PTX)-sensitive G-protein is involved in the process
HFYLPM and stromal cell-derived factor-1 (SDF-1) share the signaling via PTXsensitive G-protein, phosphatidylinositol 3-kinase (PI3K), and tyrosine kinase (Figure 2B, 4, and 5B)
Summary
T cells have a central role in the regulation of immune responses in host immunity (Goetzl et al 1992; Lee et al 1999). T cell activity can be modulated by various extracellular stimuli such as processed peptides on major histocompatibility complex molecules of antigen-presenting cells (Zoller 1988; Ha-Lee et al 2000). Among these extracellular stimuli, chemoattractants including several chemokines that regulate T cell functions have been receiving attention for a long time. On the critical role of chemoattractants in T cell function, each chemoattractant modulates chemotactic migration of the cells (Gillitzer 2001). Keeping in mind the important role of chemoattractants for T cell function, the identification of new chemoattractants and the characterization of their action mechanism are essentially needed
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