Article
SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology
Author/s | Calvo Baltanás, Fernando
García Navas, Rósula Santos, Eugenio |
Department | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2021-06-21 |
Deposit Date | 2022-12-15 |
Published in |
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Abstract | 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 ... 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. |
Funding agencies | Fundación Ramón Areces CIVP19A5942 European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III CB16/12/00352; FIS PI19/00934 Gobierno regional de Castilla y León SA264P18 UIC 076 Fundación Memoria de D. Samuel Solorzano Barruso FS/32-2020 |
Project ID. | CIVP19A5942
CB16/12/00352 FIS PI19/00934 SA264P18 UIC 076 FS/32-2020 |
Citation | Calvo Baltanás, F., García Navas, R. y Santos, E. (2021). SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology. International Journal of Molecular Sciences, 22 (12), 6613. https://doi.org/10.3390/ijms22126613. |
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