SNAP-tag Based Affinity Reagents for Proteomic Profiling of Cell Signaling
Chang, Matthew Edward Keiji
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Rapid and reliable propagation of signals through the cell is critical for all facets of cellular biology. Disrupting the fidelity of these responses leads to a number of diseases, including cancer, diabetes, and neurodegeneration. Thus, methods that allow the general characterization of signaling protein properties and function are of great practical use. The formation of multi-protein complexes is a general trait of signaling cascades and necessary for the fidelity of information transfer. The composition, spatial arrangement, and regulatory state of these signaling complexes is dynamic, and can change depending on the type and duration of the stimulus. These dynamic properties makes probing the identities and interactions of these proteins difficult. The first chapter of this thesis describes a unique chemical genetic method that can be utilized with quantitative proteomics to study different groups of signaling proteins involved in signaling. The second chapter details the profiling of a group of phosphotyrosine-recognizing domains that are important determinants of tyrosine kinase substrate selection in dynamic signaling pathways. Together, these efforts describe new proteomic tools for uncovering signaling protein function and provide insight into fidelity of tyrosine phosphorylation networks.
- Chemistry