PROTEIN-TYROSINE KINASES AND PHOSPHATASES CONTROL APOPTOSIS INDUCED BY EXTRACELLULAR ADENOSINE 5'-TRIPHOSPHATE

Extracellular ATP (ATPo) induces apoptosis and osmotic lysis in severa l cell lines. We investigated the role of protein tyrosine kinases (PT Ks) and phosphatases (PTPases) in ATPo-induced apoptosis. The PTK inhi bitor genistein prevented DNA fragmentation due to ATPo without affect ing cell lysis. Comparison of western blot analysis and in vitro kinas e assays of anti-phosphotyrosine immunopcreipitates indicated that ATP o activated PTKs whose activity was tightly regulated by PTPases. In f act, an early increase in tyrosine kinase activity was observed after ATPo-treatment and was prevented by specific PTPase inhibitors. In add ition, a rapid dephosphorylation of phosphotyrosyl residues on several proteins was detected in ATPo-treated cells. Accordingly, inhibitors of PTPases, but not of serine/threonine phosphatases, were as effectiv e as PTK-inhibitors in blocking ATPo-mediated DNA fragmentation. We de scribe the early events occurring in ATPo-induced apoptosis and sugges t a role for PTPases in cell death. (C) 1996 Academic Press, Inc.