Obligatory role of ASK1 in the apoptotic surge of K+ currents.
Apoptosis signal-regulating kinase 1 (ASK1) is a critical component of mitogen-activated protein kinase signaling pathways leading to cell death in response to cytokines and cellular stress. We use a dominant-negative (DN) form of ASK1 to show that this enzyme is necessary for the delayed surge in neuronal K+ channel activity, a required step in apoptosis. Furthermore, expression of ASK1 DN also suppresses the apoptotic increase in Kv2.1 currents transiently expressed in Chinese hamster ovary cells. Finally, over-expression of thioredoxin, an inhibitory binding partner of ASK1, is sufficient to halt the apoptotic current surge in neurons. Thus, ASK1 is an obligatory component of the pro-apoptotic modulation of K+ channels.
Aras
Mandar A
MA
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Aizenman
Elias
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016466:CHO Cells; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D006224:Cricetinae; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D013879:Thioredoxins / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D015221:Potassium Channels; D013879:Thioredoxins; D048848:MAP Kinase Kinase Kinase 5