Date of Completion

4-28-2017

Embargo Period

4-30-2017

Keywords

SH2, EGFR, Tyrosine, Phosphorylation, GRB2, KRAS, Protection, Mass Spectrometry

Major Advisor

Dr. Bruce Mayer

Associate Advisor

Dr. Arthur Gunzl

Associate Advisor

Dr. Sandra Weller

Associate Advisor

Dr. Kevin Claffey

Associate Advisor

Dr. Daniel Rosenberg

Field of Study

Molecular and Cell Biology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

The work presented in the following thesis dissertation examines the regulation of phosphotyrosine (pY) signaling, an essential cellular process that relies on the activity of three major protein classes: Tyrosine kinases (TKs) which induce pY signaling by phosphorylating tyrosine residues on substrate proteins, Protein tyrosine phosphatases (PTPs) which suppress pY signaling by removing phosphate moieties from tyrosine phosphorylated proteins and Src-Homology 2 (SH2) containing proteins which bind to tyrosine phosphorylated proteins and connect them to downstream signaling pathways. The effects of kinase localization, temporal changes in kinase activation, SH2 protein concentration, and negative feedback from downstream signaling pathways are all examined by the research presented here. This is accomplished by exploiting the Epidermal Growth Factor Receptor (EGFR), a clinically important transmembrane TK, and its SH2 protein mediated downstream pathways. Using EGFR signaling as a tool, this dissertation research attempts to define innate properties of pY signaling systems which are broadly applicable and advance our understanding of the field.

Additional Files
Table 1.1.xlsx (16 kB)
Table 1.1
Table 1.2.xlsx (754 kB)
Table 1.2
Table 2.1.xlsx (61 kB)
Table 2.1
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