Date of Award
5-2011
Document Type
Thesis
Degree Name
Master of Science (MS)
College/School
College of Science and Mathematics
Department/Program
Biology
Thesis Sponsor/Dissertation Chair/Project Chair
Quinn Vega
Committee Member
Carlos Molina
Committee Member
Sandra Adams
Abstract
The ret proto-oncogene encodes a transmembrane receptor tyrosine kinase that plays a key role in neural differentiation as well as development of the enteric nervous system and kidneys. RET is activated through interaction with members of the ligand-binding co-receptors GFRa 1-4 and its corresponding neurotrophic factors consisting of Glial Cell Line Derived Neurotrophic Factor (GDNF), neurturin (NTN), artemm (ART), or persephin (PSP) forming a heterodimer structure. Upon activation, RET undergoes autophosphorylation at select tyrosine residues in the intercellular catalytic domain, creating docking sites for proteins involved in signal transduction. While several laboratories have studied the activation of RET, little is known about how the receptor is inactivated after ligand binding. Mutations of the RET gene have been associated with several cancers such as MEN2A, MEN2B and FMTC_suggesting that the activated form of RET has somehow bypassed down regulation. In order to analyze the effect of the mutated form of RET on signal transduction and downregulation, VERO cells were transfected with wild type and activated forms of RET and the effect of RET mutations on protein degradation analyzed. The degradation studies suggest that MEN2B has a lower level of protein degradation, and that this decreased degradation rate is due to a loss of Cbl, a protein known to be involved in receptor tyrosine kinase down regulation. The connection between decreased MEN2B down regulation and the loss of Cbl provides a possible explanation for the mutant receptor’s oncogenic potential.
File Format
Recommended Citation
Maslovski, Shani Yevgeniya, "Comparison of Wild Type and Mutant Forms of RET Down-Regulation" (2011). Theses, Dissertations and Culminating Projects. 920.
https://digitalcommons.montclair.edu/etd/920