Understanding the mechanisms of cross-talk between posttranslational modifications during growth factor signalling

点击翻译按钮获取中文摘要

Cell behaviour is controlled by a complex system of cell signalling events that include post-translational modifications (PTMs) that alter the functionality, activity or stability of a protein. Cross talk between two such PTMs, phosphorylation and ubiquitination, is known to play an important role in determining specific cellular outcomes, however there is still much to learn about the interplay of these modification under certain cellular conditions. Advances in proteomics techniques have enabled large scale analysis of both phosphorylation and ubiquitination events on a global scale. Combined with quantitative techniques such as stable isotope labelling with amino acids in cell culture (SILAC), changes in the abundance of large numbers of modified peptides under specific cellular conditions can be investigated. Co-modification of peptides can be identified using concurrent enrichment strategies for both phosphorylated and ubiquitinated peptides, leading to an understanding of how these two modifications are cross-regulated. Growth factor regulated signalling pathways are reliant on post-translational modifications to control the duration of a biological response. The fibroblast growth factor (FGF) signalling pathway is one such pathway that mediates many cellular processes such as cell proliferation, differentiation and survival. Ubiquitination events are known to act in feedback loops to attenuate the signal, although these events have not been studied in a global context. The aim of this project is to study the cross talk between phosphorylation and ubiquitination in response to FGF and gain an understanding of how these modifications dynamically act together to finely tune the associated biological responses.