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*
- From the Department of Radiation Oncology, Research Laboratories, William Beaumont Hospital, Royal Oak, Michigan 48073
Abstract
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.
Footnotes
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↵* This work was supported through National Institutes of Health Grants CA 48000 and CA 44550 and William Beaumont Hospital Grant 96-03.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Dept. of Radiation Oncology Research Laboratories, William Beaumont Hospital, 3601 W. Thirteen Mile Rd., Royal Oak, MI 48073. Tel.: 810-551-2568; Fax: 810-551-2443.
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↵1 The abbreviations used are: bFGF, basic fibroblast growth factor; JNK, c-Jun N-terminal kinase; SRE, serum response element; TCF, ternary complex factor; ERK, extracellular signal-regulated kinase; GST, glutathione S-transferase; PAGE, polyacrylamide gel electrophoresis; MEKK, mitogen-activated response kinase kinase kinase.
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- Received November 7, 1996.
