Regulation of the MAPK Pathway by Raf Kinase Inhibitory Protein
Autor: | Walter Kolch, Ana Herrero, Fahd Al-Mulla, Drieke Vandamme |
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Rok vydání: | 2014 |
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Physiological MAPK/ERK pathway Cancer Research Cell signaling MAP Kinase Signaling System Chemistry Phosphatidylethanolamine Binding Protein Endogeny Plasma protein binding MAPK cascade Cell fate determination Lipid Metabolism Protein Structure Tertiary Cell biology Animals Humans Phosphorylation c-Raf Protein Binding |
Zdroj: | Critical Reviews in Oncogenesis. 19:405-415 |
ISSN: | 0893-9675 |
Popis: | The Raf kinase inhibitor protein 1 (RKIP-1) was the first reported endogenous inhibitor of Raf-1-MEK-ERK/MAPK cascade, by interfering with the phosphorylation of MEK by Raf-1. However, RKIP's functions related to the MAPK signaling are far more complex. Newer data indicate that by modulating different protein-protein interactions, RKIP is involved in fine-tuning cell signaling, modulating ERK dynamics, and regulating cross talk between different pathways. Here, we describe the molecular mechanisms by which RKIP controls MAPK signaling at different levels and vice versa and its regulation via feedback phosphorylation. We also focus on several discrepancies and questions that remain, such as the RKIP binding regulation by Raf-1 N-region phosphorylation, the possible B-Raf inhibition, and the effects of RKIP-lipid binding. We also describe how RKIP's role as key signaling modulator of many cell fate decisions leads to the fact that fine control of RKIP activity and regulation is crucial to avoid pathological processes, such as metastasis, pulmonary arterial hypertension, and heart failure. |
Databáze: | OpenAIRE |
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