Date of Award

5-2009

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

James Campanella

Committee Member

Sandra Adams

Abstract

REarranged during Transfection (RET) is a mammalian tyrosine kinase receptor involved in the signal transduction pathways during early embryonic kidney and enteric nervous system development. Activation of RET is mediated by one of the membrane associated co-receptors GFRal-4 and one of the four GFL family ligands. Following ligand binding, RET undergoes autophosphorylation followed by downstream activation of additional cell signaling proteins. However, less is understood about the down- regulation patterns of RET and of naturally occurring RET mutants and laboratory modified forms of RET. In this study, the role of the cytoplasmic domain in receptor processing and protein degradation was analyzed. In addition, protein stability rates of tyrosine autophosphorylation mutants and kinase inactive RET mutants were analyzed and compared to wild-type RET. Protein stability was assessed from 0-16 hr. The wild- type RET receptor displayed an overall decrease in the concentration of the glycosylated form, suggesting internalization of the receptor. Decrease in the membrane receptor is not observed in either the autophosphorylation mutant or the kinase inactive RET mutant. Results suggest that mutations associated with ihe intracellular domain of the receptor impede its protein modification and signaling to the membrane and further delays internalization and down-regulation.

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