The regulation of metabolic and mitogenic cellular processes is a complex system, depending on the precise function of several signalling cascades. One example is the insulin pathway, which is mediated by a group of three sequentially and structurally highly similar hormones (insulin, insulin-like growth factor (IGF) -I and -II) and their homologous tyrosine kinase receptors (IR-A, IR-B, IGF-1R). Such a high degree of homology leads to crosstalk in receptor communication, with each of the ligands triggering different biological responses. The design of insulin analogues activating primarily metabolic effects or IGF antagonists suppressing an unfavourable mitogenic response is one of the main goals in this research field, which can be facilitated by identification of the regions responsible for receptor binding. The work included in this thesis is focused on the effects on receptor interactions following the introduction of selected elements from the IGF-I primary sequence into the IGF-II molecule. In particular, these include a point mutation of Ser29 to Asn, an insertion of Gly-Ser after Arg34 , an insertion of Pro-Gln after Ser39 , or combination of both insertions. Although the IGF-II modifications described here negatively affected binding affinity towards IR-A, they did not enhance the IGF-1R...
Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:333068 |
Date | January 2014 |
Creators | Hexnerová, Rozálie |
Contributors | Tošner, Zdeněk, Obšil, Tomáš |
Source Sets | Czech ETDs |
Language | Czech |
Detected Language | English |
Type | info:eu-repo/semantics/masterThesis |
Rights | info:eu-repo/semantics/restrictedAccess |
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