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Adaptor domains in signalling proteins: phosphorylation analysis and a role in mechanosensing
Tatárová, Zuzana ; Novotný, Marian (advisor) ; Doležal, Pavel (referee)
P130Cas (Crk-associated substrate, CAS) is a multiadaptor protein important in integrin signalling where it positively regulates cell motility, invasion, proliferation and survival. CAS lacks enzymatic activity, but its binding to other signalling proteins could lead to the change of phosphorylation status of its substrate domain, which is the main mode, through which CAS takes part in regulating cell behavior. Local tensions in focal adhesions lead to an extension of CAS substrate domain, leaving phosphorylation sites more accessible for kinases, which subsequently leads to an increased CAS substrate domain phosphorylation. The CAS anchorage in focal adhesions is mediated by its SH3 domain, probably through the interactions with FAK, and also by C-terminal domain, where interaction partners are not known. The aim of my project is to find out, which proteins mediate the CAS anchorage to the focal adhesions. The elucidation of CAS anchorage to focal adhesions will contribute to the understanding of mechanosensory function of CAS. Experimental data suggest that tyrosine phosphorylation of the CAS SH3 domain plays an important role in the regulation of its binding properties. Another goal of my diploma project was to analyze the significance of tyrosine phosphorylation within SH3 domain and other...
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Adaptor domains in signalling proteins: phosphorylation analysis and a role in mechanosensing
Tatárová, Zuzana ; Novotný, Marian (advisor) ; Doležal, Pavel (referee)
P130Cas (Crk-associated substrate, CAS) is a multiadaptor protein important in integrin signalling where it positively regulates cell motility, invasion, proliferation and survival. CAS lacks enzymatic activity, but its binding to other signalling proteins could lead to the change of phosphorylation status of its substrate domain, which is the main mode, through which CAS takes part in regulating cell behavior. Local tensions in focal adhesions lead to an extension of CAS substrate domain, leaving phosphorylation sites more accessible for kinases, which subsequently leads to an increased CAS substrate domain phosphorylation. The CAS anchorage in focal adhesions is mediated by its SH3 domain, probably through the interactions with FAK, and also by C-terminal domain, where interaction partners are not known. The aim of my project is to find out, which proteins mediate the CAS anchorage to the focal adhesions. The elucidation of CAS anchorage to focal adhesions will contribute to the understanding of mechanosensory function of CAS. Experimental data suggest that tyrosine phosphorylation of the CAS SH3 domain plays an important role in the regulation of its binding properties. Another goal of my diploma project was to analyze the significance of tyrosine phosphorylation within SH3 domain and other...
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A comparison of SH3 domains' tyrosine phosporylation influence on their binding capacity
Tatárová, Zuzana ; Novotný, Marian (advisor) ; Kuthan, Martin (referee)
Understanding the impact of protein phosphorylation is very important for the formation of dynamic biological processes such as gene silencing, cell growth, differentiation or apoptosis. This work deals with the phosphorylation of a protein-interaction module known as SH3 domain and the influence of phosphorylation on its ligand-binding capacity. SH3 domain is a part of a large number of enzymes directly involved in signal transduction as well as adapter proteins without enzymatic activity. Many studies have shown the importance of tyrosine sites within SH3 domain in regulatory mechanisms of proteins by using either mutants that cannot be phosphorylated, mutants mimicking the negative charges created by phosphorylation or by evidence of in vivo phosphorylation. The work also includes bioinformatic analysis, which further expand our knowledge of SH3 phosphorylated proteins and confirms that phosphorylation of the tyrosine sites is conserved among proteins containing the SH3 domain.
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