Hepatocyte Growth Factor-induced Ras Activation Requires ERM Proteins Linked to Both CD44v6 and F-Actin
| Autor: | Helmut Ponta, Thor Kastilan, Giuseppina Pace, Véronique Orian-Rousseau, Alexandra Matzke, Peter Herrlich, Helen Morrison |
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| Rok vydání: | 2007 |
| Předmět: |
Moesin
macromolecular substances Biology Proto-Oncogene Proteins p21(ras) Ezrin Radixin Anti-apoptotic Ras signalling cascade Animals Humans Molecular Biology Cytoskeleton Glycoproteins Hepatocyte Growth Factor Microfilament Proteins Membrane Proteins Articles Cell Biology Proto-Oncogene Proteins c-met Actin cytoskeleton Actins Protein Structure Tertiary Rats Cell biology Cytoskeletal Proteins Protein Transport Hyaluronan Receptors Son of Sevenless Proteins Guanine nucleotide exchange factor HT29 Cells Protein Binding Signal Transduction |
| Zdroj: | Molecular Biology of the Cell. 18:76-83 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e06-08-0674 |
| Popis: | In several types of cells, the activation of the receptor tyrosine kinase c-Met by its ligand hepatocyte growth factor (HGF) requires the coreceptor CD44v6. The CD44 extracellular domain is necessary for c-Met autophosphorylation, whereas the intracellular domain is required for signal transduction. We have already shown that the CD44 cytoplasmic tail recruits ezrin, radixin and moesin (ERM) proteins to the complex of CD44v6, c-Met, and HGF. We have now defined the function of the ERM proteins and the step they promote in the signaling cascade. The association of ERM proteins to the coreceptor is absolutely required to mediate the HGF-dependent activation of Ras by the guanine nucleotide exchange factor Sos. The ERM proteins need, in addition, to be linked to the actin cytoskeleton to catalyze the activation of Ras. Thus, we describe here a new function of the cytoskeleton. It is part of a “signalosome” complex that organizes the activation of Ras by Sos. So far the cytoskeleton has mainly been identified as a “responder” to signal transduction. Here, we show now that F-actin acts as an “inducer” that actively organizes the signaling cascade. |
| Databáze: | OpenAIRE |
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