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Title: The roles of Ack1 in growth factor signalling and trafficking
Author: Krawczyk, Sylwia
ISNI:       0000 0004 5346 479X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2014
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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.
Supervisor: Not available Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)