P 5 - Prof. Dr. Ralf Baumeister

Prof. Dr. Ralf Baumeister

Bio3/Bioinformatics and Molecular Genetics

Schänzlestr. 1, 79104 Freiburg

Phone: +49 761 203-8350

Fax: +49 761 203-8351

baumeister@celegans.de

Homepage

Project Summary

We study the extensive interactions of Insulin/IGF (IIs) and mTORC signalling pathways to mediate organismal responses to nutritional impacts and stress. During the last funding period, we have analyzed interactions and the phosphorylation modification pattern of one main effector of both pathways, the FOXO transcription factor DAF-16, and have also shown how astrin, a novel and essential interactor of mTORC1, inhibits mTORC1 association and recruits the mTORC1 component raptor to stress granules. We identified 14 S/T phosphorylation sites in DAF-16 and have investigated their contribution to DAF-16 localization and function. We also found that the serum-and-glucocorticoid-inducible kinase SGK-1, for which DAF-16 is a direct interactor and phosphorylation substrate, is also a regulation target of DAF-16 and, in addition, a protein interactor of the mTORC2/Rictor complex to mediate diverse responses to stress. Our investigations suggest that SGK-1 may play a key role in a feedback regulation that helps to localize and activate DAF-16 and the interactions of IIs and mTORC signaling to distinguish stress and growth conditions. We suggest dissecting the functional specificity of SGK-1 interactions and regulations mediated by DAF-16 and mTORC modifications and localization dynamics using a combination of genetic and proteomic studies in cell culture and C. elegans.