RKIP regulates MAP kinase signaling in cells with defective B-Raf activity
| Autor: | Yoko Nakazawa, Lingchun Zeng, Elena Bevilacqua, Florian Kern, Manuela Baccarini, Karin Ehrenreiter, Marsha Rich Rosner, Akira Imamoto, Jyotsana Menon, Ray Menard |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Proto-Oncogene Proteins B-raf
MAPK/ERK pathway MAP Kinase Signaling System Regulator Phosphatidylethanolamine Binding Protein Article Mice Multiple Models Animals RNA Small Interfering Cells Cultured Cell Proliferation Mice Knockout Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Chemistry Raf kinase inhibitory protein Cell Biology Embryonic stem cell Cell biology Enzyme Activation Mice Inbred C57BL Proto-Oncogene Proteins c-raf MAPK activation Mitogen-activated protein kinase biology.protein RNA Interference Map kinase signaling Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | Cellular Signalling. 25:1156-1165 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2013.02.005 |
| Popis: | MAP kinase (MAPK) signaling results from activation of Raf kinases in response to external or internal stimuli. Here, we demonstrate that Raf Kinase Inhibitory Protein (RKIP) regulates the activation of MAPK when B-Raf signaling is defective. We used multiple models including mouse embryonic fibroblasts (MEFs) and primary keratinocytes from RKIP- or Raf-deficient mice as well as allografts in mice to investigate the mechanism. Loss of B-Raf protein or activity significantly reduces MAPK activation in these cells. We show that RKIP depletion can rescue the compromised ERK activation and promote proliferation, and this rescue occurs through a Raf-1 dependent mechanism. These results provide formal evidence that RKIP is a bona fide regulator of Raf-1. We propose a new model in which RKIP plays a key role in regulating the ability of cells to signal through Raf-1 to ERK in B-Raf compromised cells. |
| Databáze: | OpenAIRE |
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