V. Bronte et al., PROTEIN-TYROSINE KINASES AND PHOSPHATASES CONTROL APOPTOSIS INDUCED BY EXTRACELLULAR ADENOSINE 5'-TRIPHOSPHATE, Biochemical and biophysical research communications, 218(1), 1996, pp. 344-351
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.