Bronte V, Macino B, Zambon A, Rosato A, Mandruzzato S, Zanovello P, Collavo D
Institute of Oncology, Inter-University Center for Cancer Research, Padova, Italy.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):344-51. doi: 10.1006/bbrc.1996.0060.
Extracellular ATP (ATPo) induces apoptosis and osmotic lysis in several cell lines. We investigated the role of protein tyrosine kinases (PTKs) and phosphatases (PTPases) in ATPo-induced apoptosis. The PTK inhibitor genistein prevented DNA fragmentation due to ATPo without affecting cell lysis. Comparison of western blot analysis and in vitro kinase assays of anti-phosphotyrosine immunoprecipitates indicated that ATPo activated PTKs whose activity was tightly regulated by PTPases. In fact, an early increase in tyrosine kinase activity was observed after ATPo-treatment and was prevented by specific PTPase inhibitors. In addition, 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 effective as PTK-inhibitors in blocking ATPo-mediated DNA fragmentation. We describe the early events occurring in ATPo-induced apoptosis and suggest a role for PTPases in cell death.
