l -Selectin activates the Ras pathway via the tyrosine kinase p56 lck
| Autor: | K. Schlottmann, M. Steinhausen, Erich Gulbins, Otwin Linderkamp, K. M. Coggeshall, Florian Lang, U. Koppenhoefer, Barbara Walzog, Gillian L. Busch, Birgit Brenner |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
GTPase-activating protein
T-Lymphocytes Mast-Cell Sarcoma Transfection Jurkat cells Cell Line Mice chemistry.chemical_compound GTP-Binding Proteins Superoxides Anti-apoptotic Ras signalling cascade Animals Humans L-Selectin Phosphotyrosine Protein kinase A Multidisciplinary biology GTPase-Activating Proteins Proteins hemic and immune systems Tyrosine phosphorylation Biological Sciences Recombinant Proteins rac GTP-Binding Proteins Cell biology src-Family Kinases chemistry Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ras GTPase-Activating Proteins Calcium-Calmodulin-Dependent Protein Kinases ras Proteins biology.protein GRB2 Signal transduction Tyrosine kinase Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 93:15376-15381 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.93.26.15376 |
| Popis: | Selectins mediate rolling, the initial step of leukocyte adhesion to endothelial cells [Springer, T. A. (1995) Annu. Rev. Physiol . 57, 827–872 and Butcher, E. C. (1991) Cell 67, 1033–1036]. In this study we show that l -selectin triggering of Jurkat cells using different antibodies or glycomimetics resulted in activation of the src-tyrosine kinase p56 lck ; tyrosine phosphorylation of intracellular proteins, in particular mitogen-activating protein kinase and l -selectin; and association of Grb2/Sos with l -selectin. This association correlated with an activation of p21Ras, mitogen-activating protein kinase, Rac2, and a transient increase of O 2 − synthesis. Stimulation of the Ras pathway by l -selectin requires functional p56 lck , since p56 lck -deficient Jurkat cells (JCaM1.6) do not show tyrosine phosphorylation, association of l -selectin with Grb2/Sos, and activation of Ras upon l -selectin triggering. Transfection of JCaM1.6 cells with p56 lck reconstitutes the observed signaling events. Genetic inhibition of Ras or Rac2 prevented Rac2 stimulation and O 2 − synthesis, respectively. The specificity and the physiological significance of the observed signaling cascade is indicated by stimulation of l -selectin-transfected P815, l -selectin-positive CEM or peripheral blood lymphocytes resulting in the same activation events as in Jurkat cells. Our results point to a signaling cascade from l -selectin via p56 lck , Grb2/Sos, Ras, and Rac2 to O 2 − . |
| Databáze: | OpenAIRE |
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