An investigation into the function and signalling of the endothelial receptor tyrosine kinase Tie 1
thesisposted on 2014-12-15, 10:34 authored by Tasneem Fayez Salim
The receptor tyrosine kinase Tie1 is expressed in endothelial cells. The receptor has previously been found to have low kinase activity and poor ability to undergo autophosphorylation. The aim of this study is to define the function and signalling mechanisms used by Tie1.;This study demonstrates that the Tie1 endodomain can undergo tyrosine phosphorylation via its own kinase activity and that this is can be regulated by Tie2. Furthermore, phosphorylation is mainly confined to a carboxy-terminal fragment of the endodomain, containing the kinase domain and thus suggests possible inhibitory sequences may be present in the transmembrane and juxtamembrane regions of the Tie1.;This study also demonstrates that a recombinant Ang1 protein, COMP-Ang1, can stimulate tyrosine phosphorylation of full-length and truncated Tie1 in endothelial cells. Whether this event occurs through Tie1 alone or through Tie2 remains to be answered. This work also shows that following COMP-Ang1 stimulation. Tie1 truncation is not affected. For the first time, it has been shown that COMP-Ang1 stimulation gives rise to a heavily phosphorylated 42kDa protein, thought not to be truncated Tie1 but rather an unknown protein associated with Tie1 in endothelial cells.;Studies to define the function of Tie1 in endothelial cells show that Tie1 protects endothelial cells against apoptosis. Attempts to define whether this effect occurs in non-endothelial cells suggest that the cytoprotective function of Tie1 may be endothelial cell specific.;Work presented in this thesis demonstrates novel findings into the signalling mechanisms and function of Tie1.
Date of award2007-01-01
Author affiliationCardiovascular Sciences
Awarding institutionUniversity of Leicester