The roles of Ack1 in growth factor signalling and trafficking

Krawczyk, Sylwia (2014). The roles of Ack1 in growth factor signalling and trafficking. University of Birmingham. Ph.D.

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Abstract

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.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Heath, John KUNSPECIFIEDUNSPECIFIED
Rappoport, JoshuaUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Life & Environmental Sciences
School or Department: School of Biosciences
Funders: Cancer Research UK
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/4775

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