Abstract 58
Background: Adhesion of leukocytes to endothelial cells during the immune response to pathogens is a tightly regulated, multistep process involving selectin-mediated rolling and integrin-dependent firm adhesion. Previously, we and others have shown that L-selectin expressed on leukocytes is a signal transducing receptor in addition to its known function as mediator of leukocyte rolling. In particular, we identified activation of the small G-protein Ras upon L-selectin triggering, resulting in cytoskeletal changes and synthesis of oxygen radicals. In order to identify downstream target molecules of Ras, we tested, whether cellular stimulation of T-lymphocytes activates kinases involved in cellular stress reactions (stress activated protein kinase (SAPK) and p38-kinase (p38-K)).
Methods: In vitro kinase assays, transient transfection of inhibitory Rac and Ras.
Results: Stimulation of T-lymphocytes via L-selectin results in a Ras-dependent activation of the small G-protein Rac and SAPK but not of p38-K. L-selectin initiated activation of SAPK is mediated by src-like tyrosine kinases and the small G-protein Rac, since genetic or pharmacological inhibition of the tyrosine kinase or the Rac protein prevent stimulation of SAPK by L-selectin.
Conclusion: These data point to a novel signalling cascade from L-selectin via src-like tyrosine kinases and Rac proteins to SAPK, possibly involved in adhesion and immunomodulatory functions of leukocytes during inflammation.
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Brenner, B., Gulbins, E., Weinmann, S. et al. Pleiotropic signalling functions of the adhesion molecule L-Selectin. Pediatr Res 44, 428 (1998). https://doi.org/10.1203/00006450-199809000-00091
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DOI: https://doi.org/10.1203/00006450-199809000-00091