Date of Last Revision
2023-05-03 00:06:57
Major
Biology
Degree Name
Bachelor of Science
Date of Expected Graduation
Spring 2018
Abstract
Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as well as ligand free clusters. Despite these structures, there is still no comprehensive understanding of the role that each domain plays in ligand-dependent and ligand-free EphA2 oligomerization and activation. Here we report our investigation of the role that the intracellular domain (ICD) plays on EphA2 oligomerization. We first deleted the sterile alpha motif (SAM) domain from the C-terminus of the protein and measured oligomerization with a time-resolved, fluorescence spectroscopy method with single molecule sensitivity, called fluorescence correlation spectroscopy (FCS). Deleting the SAM domain from the intracellular domain displayed reduced mobility of EphA2, and an increased brightness. From this we concluded that the SAM domain has a role in inhibiting oligomerization of the un-liganded, full-length receptor. In future research, our aim is to investigate the role that other motifs play in receptor oligomerization. This work will have clinical applications, especially in cancers where EphA2 is mutated or overexpressed.
Research Sponsor
Dr. Jim Holda and Dr. Adam Smith
First Reader
Dr. Leah Shriver
Second Reader
Dr. Sailaja Paruchuri
Recommended Citation
Lingerak, Ryan W., "Altering Oligomerization of EphA2 via Mutations in the Intracellular Domain" (2018). Williams Honors College, Honors Research Projects. 574.
https://ideaexchange.uakron.edu/honors_research_projects/574
Included in
Biochemistry Commons, Biophysics Commons, Cancer Biology Commons, Molecular Biology Commons