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Título: | Sos2 comes to the fore: Differential functionalities in physiology and pathology |
Autor: | Baltanás, Fernando C. CSIC ORCID CVN; García-Navas, Rósula CSIC ORCID CVN; Santos de Dios, Eugenio CSIC ORCID CVN | Palabras clave: | Son of sevenless SOS1 SOS2 RAS signaling GEFs |
Fecha de publicación: | 2021 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | International Journal of Molecular Sciences 22(12): 6613 (2021) | Resumen: | The SOS family of Ras-GEFs encompasses two highly homologous and widely expressed members, SOS1 and SOS2. Despite their similar structures and expression patterns, early studies of constitutive KO mice showing that SOS1-KO mutants were embryonic lethal while SOS2-KO mice were viable led to initially viewing SOS1 as the main Ras-GEF linking external stimuli to downstream RAS signaling, while obviating the functional significance of SOS2. Subsequently, different genetic and/or pharmacological ablation tools defined more precisely the functional specificity/redundancy of the SOS1/2 GEFs. Interestingly, the defective phenotypes observed in concomitantly ablated SOS1/2-DKO contexts are frequently much stronger than in single SOS1-KO scenarios and undetectable in single SOS2-KO cells, demonstrating functional redundancy between them and suggesting an ancillary role of SOS2 in the absence of SOS1. Preferential SOS1 role was also demonstrated in different RASopathies and tumors. Conversely, specific SOS2 functions, including a critical role in regulation of the RAS–PI3K/AKT signaling axis in keratinocytes and KRAS-driven tumor lines or in control of epidermal stem cell homeostasis, were also reported. Specific SOS2 mutations were also identified in some RASopathies and cancer forms. The relevance/specificity of the newly uncovered functional roles suggests that SOS2 should join SOS1 for consideration as a relevant biomarker/therapy target. | Descripción: | © 2021 by the authors. | Versión del editor: | http://dx.doi.org/10.3390/ijms22126613 | URI: | http://hdl.handle.net/10261/262153 | DOI: | 10.3390/ijms22126613 | ISSN: | 1661-6596 | E-ISSN: | 1422-0067 |
Aparece en las colecciones: | (IBMCC) Artículos |
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SOS2 Comes to the Fore_Baltanas_PV_Art2021.pdf | 642,54 kB | Adobe PDF | Visualizar/Abrir |
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