- 作者: Lawrence S. Chin Susan F. Murray David H. Harter Patrick F. Doherty Satyendra K. Singh
- 作者服務機構: Department of Neurosurgery and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Md., USA
- 中文摘要: --
- 英文摘要: The dual signal hypothesis of apoptosis holds that acommon signal can activate both apoptotic and prolifer-ative pathways. The fate of a cell is dependent on whichof these two pathways predominates. In the MAPK fami-1y of kinases, ERK and JNK have been proposed tomediate apoptosis whereas the PI3K-stimulated kinase,Akt/PKB, has been shown to inhibit apoptosis. The objectof this study was to determine the role of these kinases ina glioma model of apoptosis. We have previously shownthat K252a induces apoptosis and inhibits kinase activity.In this study we confirm these results and show that theprotein tyrosine phosphatase inhibitor sodium vanadateactivates ERK, JNK and Akt/PKB, but does not stimulateproliferation. Vanadate did protect T98G cells fromK252a-induced apoptosis, an effect that was abolishedby addition of the PI3K inhibitor wortmannin. This sug-gests that PI3K and Akt/PKB may be responsible formediating vanadate's protective effect on glioma cells.We conclude that the intracellular balance between pro-tein phosphorylation pathways is a critical determinantof both cell proliferation and cell death.
- 中文關鍵字: --
- 英文關鍵字: Glioma. Apoptosis. Vandat. Akt. PKB