Indirect recruitment of the signalling adaptor Shc to the fibroblast growth factor receptor 2 (FGFR2)

International audienceThe adaptor protein Shc plays an important role in the activation of signalling pathways downstream of receptor tyrosine kinases (RTKs) regulating diverse cellular functions such as differentiation, adhesion, migration and mitogenesis. Despite being phosphorylated downstream of members of the fibroblast growth factor receptor (FGFR) family, a direct interaction of Shc with this receptor family has not been described to date. Various studies have suggested potential binding sites for the Shc PTB and/or SH2 domains on the FGFR1, but no interaction of full length Shc with these sites has been reported in vivo. We investigated the importance of the SH2 and PTB domains in recruitment of Shc to the FGFR2(IIIc) to characterise the interaction of these two proteins. Confocal microscopy revealed extensive co-localisation of Shc with the FGFR2. The PTB domain was identified as the critical component of Shc mediating membrane localisation. Data from fluorescent lifetime imaging microscopy (FLIM) revealed that the interaction of Shc and FGFR2 is indirect, suggesting that the adaptor protein forms part of a signalling complex containing the receptor. We identified the non-receptor tyrosine kinase Src as a protein potentially mediating formation of such a ternary complex. Although an interaction between Src and Shc has been described previously, we implicate the Shc SH2 domain as a novel mediator of this association. The recruitment of Shc to the FGFR2 via an indirect mechanism provides new insight into the regulation of protein assembly and activation of various signalling pathways downstream of this RTK

Digital Interventions for Mental Disorders:Key Features, Efficacy, and Potential for Artificial Intelligence Applications

Mental disorders are highly prevalent and often remain untreated. Many limitations of conventional face-to-face psychological interventions could potentially be overcome through Internet-based and mobile-based interventions (IMIs). This chapter introduces core features of IMIs, describes areas of application, presents evidence on the efficacy of IMIs as well as potential effect mechanisms, and delineates how Artificial Intelligence combined with IMIs may improve current practices in the prevention and treatment of mental disorders in adults. Meta-analyses of randomized controlled trials clearly show that therapist-guided IMIs can be highly effective for a broad range of mental health problems. Whether the effects of unguided IMIs are also clinically relevant, particularly under routine care conditions, is less clear. First studies on IMIs for the prevention of mental disorders have shown promising results. Despite limitations and challenges, IMIs are increasingly implemented into routine care worldwide. IMIs are also well suited for applications of Artificial Intelligence and Machine Learning, which provides ample opportunities to improve the identification and treatment of mental disorders. Together with methodological innovations, these approaches may also deepen our understanding of how psychological interventions work, and why. Ethical and professional restraints as well as potential contraindications of IMIs, however, should also be considered. In sum, IMIs have a high potential for improving the prevention and treatment of mental health disorders across various indications, settings, and populations. Therefore, implementing IMIs into routine care as both adjunct and alternative to face-to-face treatment is highly desirable. Technological advancements may further enhance the variability and flexibility of IMIs, and thus even further increase their impact in people’s lives in the future