Hypoglycemia-induced c-Jun phosphorylation is mediated by c-Jun N-terminal kinase 1 and Lyn kinase in drug-resistant human breast carcinoma MCF-7/ADR cells.
We studied the signal transduction mechanism that is involved in c-Jun phosphorylation evident after glucose deprivation in MCF-7/ADR cells. Glucose deprivation caused an immediate increase in tyrosine phosphorylation in MCF-7/ADR cells and specifically activated Lyn kinase, a src family tyrosine kinase. In addition, hypoglycemic treatment strongly activated c-Jun N-terminal kinase 1 (JNK1), leading to the phosphorylation and activation of c-Jun. Experiments with Lyn antisense oligonucleotides demonstrated that Lyn kinase activation was responsible for the activation of JNK1 but not extracellular signal-regulated kinase. We also observed glucose deprivation-induced Ras activation in MCF-7/ADR cells. These results indicate a possible Ras-dependent signaling pathway involving Lyn kinase and JNK1, which leads to the glucose deprivation-induced responses in MCF-7/ADR cells.
Liu
X
X
Department of Radiation Oncology, Research Laboratories, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.
Gupta
A K
AK
Corry
P M
PM
Lee
Y J
YJ
D001943:Breast Neoplasms; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007003:Hypoglycemia; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D004317:Doxorubicin; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins