L-selectin activates JNK via src-like tyrosine kinases and the small G-protein Rac.
Selectin and alpha 4 beta 7-integrins have been shown to mediate transient leucocyte interactions with endothelial cells which is a crucial step in the initial immune response to pathogens. We have previously shown that stimulation of T lymphocytes via L-selectin results in activation of a signalling cascade from the L-selectin molecule via the tyrosine kinase p56lck and tyrosine phosphorylation of L-selectin to the stimulation of p21Ras and Rac proteins. In the present study we demonstrate that stimulation of Jurkat T lymphocytes via L-selectin results in an activation of Jun N-terminal kinase (JNK) but not of p38-K. L-selectin-initiated activation of JNK is mediated by src-like tyrosine kinases and the small G-protein Rac 1/2, since genetic or pharmacological inhibition of p56lck or Rac proteins prevent the stimulation of JNK by L-selectin. Thus, the data point to a novel signalling cascade from L-selectin via src-like tyrosine kinases and Rac proteins to JNK.
Brenner
B
B
Department of Paediatrics, University of Heidelberg, Germany.
Weinmann
S
S
Grassmé
H
H
Lang
F
F
Linderkamp
O
O
Gulbins
E
E
D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019041:L-Selectin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins
D019041:L-Selectin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins