TY - JOUR
T1 - Protein tyrosine kinases and phosphatases control apoptosis induced by extracellular adenosine 5′-triphosphate
AU - Bronte, Vincenzo
AU - Macino, Beatrice
AU - Zambon, Annalisa
AU - Rosato, Antonio
AU - Mandruzzato, Susanna
AU - Zanovello, Paola
AU - Collavo, Dino
PY - 1996/1/5
Y1 - 1996/1/5
N2 - Institute of Oncology, Chair of Immunology, Inter-University Center for Cancer Research, Via Gattamelata 64, Padova 35128, Italy 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.
AB - Institute of Oncology, Chair of Immunology, Inter-University Center for Cancer Research, Via Gattamelata 64, Padova 35128, Italy 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.
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U2 - 10.1006/bbrc.1996.0060
DO - 10.1006/bbrc.1996.0060
M3 - Article
C2 - 8573158
AN - SCOPUS:0030044904
VL - 218
SP - 344
EP - 351
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -