10.4225/03/58a52fcae6e4a Henstridge, Michelle Ann Michelle Ann Henstridge Localised control of Torso receptor tyrosine kinase activation in Drosophila terminal patterning Monash University 2017 Drosophila thesis(doctorate) Embryonic patterning monash:146335 ethesis-20141204-134042 2014 Signalling Restricted access 1959.1/1122179 Commendation Vice-Chancellor’s Commendation for Doctoral Thesis Excellence 2017-02-16 04:51:21 Thesis https://bridges.monash.edu/articles/thesis/Localised_control_of_Torso_receptor_tyrosine_kinase_activation_in_Drosophila_terminal_patterning/4657960 Receptor tyrosine kinases (RTKs) control many signalling pathways that regulate fundamental cell biological processes such as proliferation, differentiation and survival. The controlled activation of RTKs is thus crucial, and depends on both the presence of the receptor at the cell surface and on the availability of its ligand. In Drosophila, the RTK Torso (Tor) is responsible for the specification of the most anterior and posterior regions of the developing embryo. Tor is distributed ubiquitously on the plasma membrane of the embryo but signals only at the poles due to the localised availability of its ligand Trunk (Trk). While it is understood that Tor activation is mediated by Torso-like (Tsl), a membrane attack complex/ perforin-like (MACPF) protein present only at the embryo poles, the mechanism by which this occurs and the precise role of Tsl remains unclear. It has long been presumed that Trk must be cleaved in order to bind Tor, and that these proteolytic events are controlled by Tsl. However, no protease involved in terminal patterning has previously been identified, nor has a cleaved Trk species been detected. To address these problems, functional tagged forms of Trk were generated and used to show that Trk is proteolytically cleaved and this is essential for Tor activation. Unexpectedly, Trk cleavage patterns were found to be unaltered in tsl null mutants, suggesting that Tsl functions post proteolytic processing of Trk to control localised terminal patterning. <div><br></div><div>Awards: Vice-Chancellor’s Commendation for Doctoral Thesis Excellence in 2014.</div>