Inhibition of phosphatidylserine synthesis during Jurkat T cell activation. The phosphatase inhibitor, sodium ortho-vanadate bypasses the CD3/T cell receptor-induced second messenger signaling pathway.
Sodium ortho-vanadate (Na3VO4), an inhibitor of protein tyrosine phosphatase, induces a rapid (15 min) and strong inhibition of phosphatidylserine synthesis with an IC50 = 100 microM. The mode of action of Na3VO4 was compared to that of CD3 mAbs. It was found that Na3VO4 bypasses the major CD3-induced T cell activation signals including protein tyrosine phosphorylation, p56lck activation and the generation of second messengers including inositol phosphates and its subsequent Ca2+ mobilization as well as diacylglycerol production. These facts were confirmed by using a panel of Jurkat clones that differs by the expression of either tyrosine kinases involved in the CD3-induced T cell activation pathway such as p56lck, p72syk and ZAP-70 or some cell surface receptors such as the CD3/TCR complex or the CD45 phosphatase.
Pelassy
C
C
INSERM U343, Hôpital de l'Archet, Nice, France.
Breittmayer
J P
JP
Aussel
C
C
D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000032:analysis; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D010718:Phosphatidylserines / Q000096:biosynthesis*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015290:Second Messenger Systems; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004075:Diglycerides; D010718:Phosphatidylserines; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D014638:Vanadates; D015544:Inositol 1,4,5-Trisphosphate; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010744:Phosphoric Monoester Hydrolases; D000252:Calcium-Transporting ATPases; D002118:Calcium