Effect of glucose concentration on activation of the ASK1-SEK1-JNK1 signal transduction pathway.
Recently, acute total glucose deprivation has been shown to cause activation of ASK1-MEK-MAPK signal transduction and dissociation of glutaredoxin (GRX) from apoptosis signal-regulating kinase 1 (ASK1). In this study, we investigated whether clinically relevant concentrations (0.01-0.1 mM) of glucose promote ASK1 activation. We observed that a prominent activation of JNK1 occurred at a glucose concentration less than or equal to 0.01 mM. Similar to JNK1 activation, we also observed that low glucose-induced ASK1 activation, dissociation of GRX and thioredoxin (TRX) from ASK1, dimerization of ASK1, and association of Daxx and TRAF2 with ASK1 significantly occurred at a glucose concentration less than or equal to 0.01 mM.
Song
Jae J
JJ
Department of Surgery, University of Pittsburgh, The Hillman Cancer Center G.5a, 5117 Centre Ave., Pittsburgh, PA 15213, USA. leeyj@msx.upmc.edu
Lee
Yong J
YJ
D000256:Adenoviridae / Q000235:genetics; D019281:Dimerization; D004789:Enzyme Activation / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology*; D054477:Glutaredoxins; D006801:Humans; D015151:Immunoblotting; D048670:MAP Kinase Kinase 4; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010088:Oxidoreductases; D011471:Prostatic Neoplasms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2; D013879:Thioredoxins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism
C516005:GLRX protein, human; D054477:Glutaredoxins; D011506:Proteins; D047992:TNF Receptor-Associated Factor 2; D014764:Viral Proteins; D013879:Thioredoxins; D010088:Oxidoreductases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D005947:Glucose