Mölling
Fakultäten » Medizinische Fakultät » Medizinische Virologie, Institut für » Prof. Dr. Karin Mölling (emeritiert) » Mölling
Completed research project
| Title / Titel | The Raf Kinase in Signal Transduction of normal and tumor cells | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | C-Raf is the cellular homologue of a retroviral oncogene, which we identified as serine/threonine specific protein kinase in 1984. It is essential in signal transduction from growth factor stimulated receptor tyrosine kinases to the nucleus. It is constitutively activated in cancer and essential during development and differentiation. By subtractive hybridisation we have determinated a number of Raf-activated genes in cancer cells. A focus has been a Raf-Akt crosstalk, which has been published in two Science papers in 1999 and several follow-up papers. The balance of the two kinases decides on the cellular outcome, proliferation or differentiation. Using the yeast-two-hybrid system we identified a number of new protein interaction partners, in particular of Akt and PKC. These two kinases interact with a novel propeller-type protein in response to insulin. A recent emphasis has been put on the role of Raf in non-proliferative situations. For the maintenance of epithelial or polar cells quiescence kinases such as Bcr downregulate the Raf-MEK-ERK pathway. Hereby tight-junction proteins such as AF-6 contribute to the formation of monolayers. Some oncoproteins are under investigation for their down- tuning by PDZ proteins, which has also antiproliferative consequences. The c-Src protein, the homologue of v-Src, is negatively regulated by a PDZ protein according to our recent studies. Bcr is a tumor-suppressor gene, which we recently showed to downregulate b-catenin in quiescent cells. Another signaling project was performed with the HIV coreceptor CCR5 for which a new protein interaction partner JM4 has been identified. It appears to play a role in receptor transport from the Golgi to the plasma membrane. | ||
| Keywords / Suchbegriffe | Molecular Medicine, Tumor Research, HIV signaling | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 1985 to Jan 2008 |