AbstractsBiology & Animal Science

The roles of Ack1 in growth factor signalling and trafficking

by Sylwia Krawczyk

Institution: University of Birmingham
Department: School of Biosciences
Year: 2014
Keywords: R Medicine (General); RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Record ID: 1406722
Full text PDF: http://etheses.bham.ac.uk/4775/


Growth factor signalling controls multiple cellular functions, such as cell growth, proliferation, migration and cell survival, and misregulation of growth factor signalling has been shown to promote cancer development and progression. The study presented within this thesis focuses on the functions of a non-receptor tyrosine kinase Ack1 (Activated Cdc42-associated kinase 1, TNK2) in epidermal growth factor (EGF) receptor (EGFR) trafficking. This study reveals that Ack1 subcellular localization greatly depends on EGF availability. Furthermore, this work also identifies a potential role for Ack1 in a non-canonical degradative pathway through its associations with several autophagosomal proteins. Analyses of a panel of the Ack1 deletion mutants further reveal key mechanistic aspects of these associations and identify the Ack1 domains which are required for these to occur. Finally, a mass spectrometric approach has been applied which identifies novel post-translational modification sites within Ack1, and in combination with stable isotope labelling of amino acids in cell culture (SILAC), has allowed for characterisation of novel Ack1 interactors.