The CD40 ligand directly activates T-lymphocytes via tyrosine phosphorylation dependent PKC activation.
The activation of B-lymphocytes depends critically on the interaction of the CD40 receptor with its ligand. Here, we provide evidence that the CD40 ligand (CD40L) also functions as a direct stimulatory molecule for T-lymphocytes. Activation of T-lymphocytes via CD40L induces tyrosine phosphorylation of cellular proteins including PLC gamma. Tyrosine phosphorylation of PLC gamma correlates with an IP3- and Ca(2+)-release and an activation of PKC. Inhibition of src-like tyrosine kinases by Herbimycin A prevents these activation events suggesting a crucial role of tyrosine phosphorylation in T-lymphocyte activation via CD40L.
Brenner
B
B
Department of Physiology, University of Tuebingen, Germany.
Koppenhoefer
U
U
Lepple-Wienhues
A
A
Grassmé
H
H
Müller
C
C
Speer
C P
CP
Lang
F
F
Gulbins
E
E
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D016227:Benzoquinones; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D016227:Benzoquinones; D019013:CD40 Antigens; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D008024:Ligands; D008562:Membrane Glycoproteins; D011809:Quinones; D023201:CD40 Ligand; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D051966:Phospholipase C gamma