The P34G mutation reduces the transforming activity of K-Ras and N-Ras in NIH 3T3 cells but not of H-Ras
| Autor: | Susana García-Vargas, Natalia Martínez, Angeles Juarranz, Rocío Jorge, José Luis Oliva, Antonio Castrillo, Natasha Zarich, Marta Azañedo, Silvia Gutiérrez-Eisman, J. Silvio Gutkind, Lisardo Boscá, José M. Rojas |
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| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España) |
| Rok vydání: | 2018 |
| Předmět: |
rac1 GTP-Binding Protein
MAPK/ERK pathway Scaffold protein Proto-Oncogene Proteins c-akt Mutant Gene Expression Protein Serine-Threonine Kinases Biology Transfection Biochemistry Mice Phosphatidylinositol 3-Kinases Structure-Activity Relationship Proto-Oncogene Proteins Anti-apoptotic Ras signalling cascade ral Guanine Nucleotide Exchange Factor Phospholipase D Animals Humans Protein Isoforms Withdrawals/Retractions Molecular Biology ets-Domain Protein Elk-1 Mitogen-Activated Protein Kinase 1 Genetics Binding Sites Mitogen-Activated Protein Kinase 3 Effector Cell Biology Protein-Serine-Threonine Kinases Cell biology DNA-Binding Proteins Enzyme Activation Proto-Oncogene Proteins c-raf Genes ras Mutation NIH 3T3 Cells ras Proteins ral GTP-Binding Proteins Mitogen-Activated Protein Kinases Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 1083-351X |
| Popis: | Retraction in: The P34G mutation reduces the transforming activity of K-Ras and N-Ras in NIH 3T3 cells but not of H-Ras. [J Biol Chem. 2018] Ras proteins (H-, N-, and K-Ras) operate as molecular switches in signal transduction cascades controlling cell proliferation, differentiation, or apoptosis. The interaction of Ras with its effectors is mediated by the effector-binding loop, but different data about Ras location to plasma membrane subdomains and new roles for some docking/scaffold proteins point to signaling specificities of the different Ras proteins. To investigate the molecular mechanisms for these specificities, we compared an effector loop mutation (P34G) of three Ras isoforms (H-, N-, and K-Ras4B) for their biological and biochemical properties. Although this mutation diminished the capacity of Ras proteins to activate the Raf/ERK and the phosphatidylinositol 3-kinase/AKT pathways, the H-Ras V12G34 mutant retained the ability to cause morphological transformation of NIH 3T3 fibroblasts, whereas both the N-Ras V12G34 and the K-Ras4B V12G34 mutants were defective in this biological activity. On the other hand, although both the N-Ras V12G34 and the K-Ras4B V12G34 mutants failed to promote activation of the Ral-GDS/Ral A/PLD and the Ras/Rac pathways, the H-Ras V12G34 mutant retained the ability to activate these signaling pathways. Interestingly, the P34G mutation reduced specifically the N-Ras and K-Ras4B in vitro binding affinity to Ral-GDS, but not in the case of H-Ras. Thus, independently of Ras location to membrane subdomains, there are marked differences among Ras proteins in the sensitivity to an identical mutation (P34G) affecting the highly conserved effector-binding loop. This work was supported in part by Programa General del Conocimiento (BMC2001-0057), Intramural Instituto de Salud Carlos III (ISCIII) (01/16), and SAF2003-02604 (Ministerio de Ciencia y Tecnología) grants (to J. M. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Sí |
| Databáze: | OpenAIRE |
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