L-selectin stimulates the neutral sphingomyelinase and induces release of ceramide.
Selectins have been shown to be crucial in the rolling process of leukocytes during lymphocyte homing and in the early phase of inflammatory processes. Recently, we and others have shown that binding of L-selectin to its ligands correlates with a rapid induction of several intracellular signaling molecules, in particular, Src-like tyrosine kinases, MAP-kinases, Jun NH2-terminal kinase, the small G-proteins Ras and Rac, and a release of Ca2+ in leukocytes. Here, we demonstrate the activation of a novel signaling pathway by L-selectin. Stimulation of Jurkat T-lymphocytes via L-selectin results in an increase of neutral sphingomyelinase activity. This activity correlates with a consumption of cellular sphingomyelin and a release of ceramide. The activation of the neutral sphingomyelinase by L-selectin does not depend on tyrosine kinase activity and, therefore, represents an alternative and novel pathway to stimulate lymphocytes via L-selectin.
Department of Neonatology, University of Tuebingen, Ruemelinstrasse 23, Tuebingen, 72070, Germany.
B
B
Brenner
H U
HU
Grassmé
C
C
Müller
F
F
Lang
C P
CP
Speer
E
E
Gulbins
D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000494:pharmacology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D002518:Ceramides; D019041:L-Selectin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013108:Sphingomyelin Phosphodiesterase; D019311:Staurosporine