Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells
| العنوان: | Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells |
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| المؤلفون: | Anne W. Hamburger, W. M. Luo, Rakesh Kumar, Amjad Hossain Talukder, Yuexing Zhang, D. Akinmade |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cancer Research, Breast Neoplasms, Biology, Transfection, Substrate Specificity, 03 medical and health sciences, breast cancer, 0302 clinical medicine, PAK1, Tumor Cells, Cultured, medicine, Humans, ERBB3, Protein phosphorylation, skin and connective tissue diseases, Adaptor Proteins, Signal Transducing, Cell Proliferation, 030304 developmental biology, 0303 health sciences, phosphorylation, Kinase, RNA-Binding Proteins, Cancer, Genetics and Genomics, medicine.disease, 3. Good health, Tamoxifen, p21-Activated Kinases, Oncology, Ebp1, 030220 oncology & carcinogenesis, Mutation, PA2G4, Cancer research, Phosphorylation, Breast disease, Protein Binding, medicine.drug |
| الوصف: | The ErbB3 binding protein (Ebp1) is a transcriptional corepressor that inhibits the activity of proliferation-associated genes and the growth of human breast cancer cell lines. Treatment of breast cancer cells with the ErbB3 ligand heregulin (HRG) results in increased phosphorylation of Ebp1 and transcriptional repression. The p21-activated serine/threonine kinase 1 (PAK1), which plays an important role in breast cancer progression and resistance to the anti-oestrogen tamoxifen, is also activated by HRG. We therefore examined the ability of PAK1 to phosphorylate and regulate the function of Ebp1. We found that PAK1 phosphorylated Ebp1 in vitro and mapped the phosphorylation site to threonine 261. Both HRG treatment and expression of a constitutively activated PAK1 in MCF-7 breast cancer cells enhanced threonine phosphorylation of Ebp1. In MCF-7 cells, ectopically expressed Ebp1 bound endogenous PAK1 and this association was enhanced by treatment with HRG. Mutation of the PAK1 phosphorylation site to glutamic acid, mimicking a phosphorylated state, completely abrogated the ability of Ebp1 to repress transcription, inhibit growth of breast cancer cell lines and contribute to tamoxifen sensitivity. These studies demonstrate for the first time that Ebp1 is a substrate of PAK1 and the importance of the PAK1 phosphorylation site for the functional activity of Ebp1 in breast cancer cells. |
| تدمد: | 1532-1827 0007-0920 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b828bc29846cc605e7fa4aa2ea0a465cTest https://doi.org/10.1038/sj.bjc.6604261Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b828bc29846cc605e7fa4aa2ea0a465c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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