Inhibition of phosphatidylserine synthesis during Jurkat T cell activation- The phosphatase inhibitor, sodium ortho-vanadate bypasses the CD3/T cellreceptor-induced second messenger signaling pathway

Sodium ortho-vanadate (Na3VO4), an inhibitor of protein tyrosine phosphatas e, induces a rapid (15 min) and strong inhibition of phosphatidylserine syn thesis with an IC50 = 100 mu M. The mode of action of Na3VO4 was compared t o that of CD3 mAbs. It was found that Na3VO4 bypasses the major CD3-induced T cell activation signals including protein tyrosine phosphorylation, p56l ck activation and the generation of second messengers including inositol ph osphates and its subsequent Ca2+ mobilization as well as diacylglycerol pro duction. These facts were confirmed by using a panel of Jurkat clones that differs by the expression of either tyrosine kinases involved in the CD3-in duced T cell activation pathway such as p56(lck), p72(syk) and ZAP-70 or so me cell surface receptors such as the CD3/TCR complex or the CD45 phosphata se.