MNK1 and MNK2 Regulation in HER2-overexpressing Breast Cancer Lines
| Autor: | Thomas W. Sturgill, Carol A. Chrestensen, Andrew Eschenroeder, Jacquelyn K. Shuman, Mark T. Worthington, Hermann Gram |
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| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Receptor ErbB-2 p38 mitogen-activated protein kinases Breast Neoplasms Protein Serine-Threonine Kinases Biology p38 Mitogen-Activated Protein Kinases Biochemistry Enzyme activator Cell Line Tumor Humans Phosphorylation skin and connective tissue diseases Molecular Biology Regulation of gene expression Kinase Intracellular Signaling Peptides and Proteins Cell Biology Enzyme Activation Gene Expression Regulation Neoplastic SKBR3 Immunology Cancer research Tyrosine Female Signal transduction Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 282:4243-4252 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m607368200 |
| Popis: | MAPK-interacting protein kinases 1 and 2 (MNK1 and MNK2) function downstream of p38 and ERK MAPK, but there are large gaps in our knowledge of how MNKs are regulated and function. As proteins activated in the HER2/Ras/Raf/ERK pathway, the MNKs are of potential interest in HER2-overexpressing cancers. We utilized a panel of breast cell lines (HCC1419, AU565, SKBR3, MCF7, and MCF10A), three of which overexpress HER2, to characterize the amounts and activation status of MNKs and other pathway enzymes (ERKs and RSKs) in these cells. We generated a phosphospecific antibody to Thr(P)-214 in the T-loop of MNKs and found that phosphorylations of both Thr-209 and Thr-214 in human MNK1 are required for activation. Increased phosphorylation and activity of the MNKs correlate with HER2 overexpression, and inhibition of the MNKs reduces colony formation in soft agar. Our work identifies the MNKs as potential therapeutic targets for breast cancer treatments. |
| Databáze: | OpenAIRE |
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