Evidence for a novel function of the CD40 ligand as a signalling molecule in T-lymphocytes.
The interaction of the CD40 receptor with its ligand has been shown to be crucial for the activation of B-lymphocytes. Here, we provide evidence that the pg39 molecule/CD40 ligand (gp39/CD40L) also functions as a stimulatory molecule for T-lymphocytes. Activation of T-lymphocytes via gp39/CD40L induced a strong activation of Jun-N-terminal kinase (JNK) and p38-K. Activation of these kinases correlates with a stimulation of Rac1 and inhibition of Rac1 prevents gp39/CD40L triggered JNK/p38-K activation. Further, cellular stimulation via the CD40 ligand results in tyrosine phosphorylation of cellular proteins and the activation of p56(lck). Inhibition of src-like kinases inhibits Rac1 as well as JNK/p38-K stimulation suggesting a signalling cascade from the gp39/CD40L via p56(lck) and Rac1 to JNK/p38-K.
Brenner
B
B
Department of Physiology, University of Tübingen, Germany.
Koppenhoefer
U
U
Grassmé
H
H
Kun
J
J
Lang
F
F
Gulbins
E
E
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000201:enzymology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D015703:Antigens, CD; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; 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; D048051:p38 Mitogen-Activated Protein Kinases