Activation of Ras Requires the ERM-Dependent Link of Actin to the Plasma Membrane
| Autor: | Ingmar Scholl, Katja J. Geißler, Tobias Sperka, Peter Herrlich, Helen Morrison, Ignacio Rubio, Ulrike Merkel |
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| Rok vydání: | 2011 |
| Předmět: |
Cytoskeletal proteins
Membrane proteins Guanine nucleotide exchange factors Ras signaling NIH 3T3 cells Immunoprecipitation Small interfering RNAs Coreceptors lcsh:Medicine Son of Sevenless Biochemistry Mice Ezrin Radixin Anti-apoptotic Ras signalling cascade Molecular Cell Biology Tyrosine Kinase Signaling Cascade Signaling in Cellular Processes Membrane Receptor Signaling Receptors Platelet-Derived Growth Factor lcsh:Science Cytoskeleton Multidisciplinary biology Microfilament Proteins Cellular Structures Signaling Cascades Cell biology Thiazolidines ras Guanine Nucleotide Exchange Factors GRB2 Signal transduction Allosteric Site Research Article Signal Transduction Protein Binding Moesin Ras Signaling macromolecular substances Signaling Pathways Models Biological Cell Line Growth Factors Animals Humans Protein Interactions Biology Cell Membrane lcsh:R Proteins Membrane Proteins biochemical phenomena metabolism and nutrition Bridged Bicyclo Compounds Heterocyclic Actins Protein Structure Tertiary Rats Enzyme Activation Cytoskeletal Proteins Membrane protein Son of Sevenless Proteins Biocatalysis ras Proteins biology.protein Mutant Proteins lcsh:Q |
| Zdroj: | PLoS ONE, Vol 6, Iss 11, p e27511 (2011) PLOS ONE, 6(11): e27511 PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0027511 |
| Popis: | Background Receptor tyrosine kinases (RTKs) participate in a multitude of signaling pathways, some of them via the small G-protein Ras. An important component in the activation of Ras is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. Principal Findings We can now demonstrate that the activation of Ras requires, in addition, the essential participation of ezrin, radixin and/or moesin (ERM), a family of actin-binding proteins, and of actin. Disrupting either the interaction of the ERM proteins with co-receptors, down-regulation of ERM proteins by siRNA, expression of dominant-negative mutants of the ERM proteins or disruption of F-actin, abolishes growth factor-induced Ras activation. Ezrin/actin catalyzes the formation of a multiprotein complex consisting of RTK, co-receptor, Grb2, SOS and Ras. We also identify binding sites for both Ras and SOS on ezrin; mutations of these binding sites destroy the interactions and inhibit Ras activation. Finally, we show that the formation of the ezrin-dependent complex is necessary to enhance the catalytic activity of SOS and thereby Ras activation. Conclusions Taking these findings together, we propose that the ERM proteins are novel scaffolds at the level of SOS activity control, which is relevant for both normal Ras function and dysfunction known to occur in several human cancers. |
| Databáze: | OpenAIRE |
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