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osu1054165285.pdf (4.92 MB)
ETD Abstract Container
Abstract Header
Regulation of vein, an activating ligand of the drosophila EGF receptor
Author Info
Wang, Shu-Huei
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1054165285
Abstract Details
Year and Degree
2003, Doctor of Philosophy, Ohio State University, Molecular Genetics.
Abstract
Signaling through the EGF receptor (EGFR) family of receptor tyrosine kinases is important in both normal development and in disease processes. In Drosophila, there is a single EGF receptor and multiple ligands. I show that EGFR signaling stimulated by its activating ligand, Vein, has a fundamental role in regulating two of these cell fate choices: 1) Vn/EGFR signaling directs cells to become notum by antagonizing wing development and by activating notum-specifying genes. 2) Vn/EGFR signaling directs cells to become part of the dorsal compartment by induction of apterous, the dorsal selector gene, and consequently also controls wing development, which depends upon an interaction between dorsal and ventral cells. To understand the control of Vn activity, I investigated transcriptional and post-translational regulation. I analyzed the transcriptional regulation of vn expression in both early and late wing discs using enhancer-reporter study and sequence comparison in Drosophila species. Using the yeast two hybrid system, I identified an interaction between gutfeeling (guf), a homologue of the vertebrate ornithine decarboxylase antizyme (OAZ), and the Ig domain of Vn. This interaction was confirmed in in vitro binding assays and by co-immunoprecipitation. In mammals, OAZ has been shown to bind to Ornithine decarboxylase (ODC) and Smad1, and targets these proteins for degradation by the 26S proteasome in an ubiquitin-independent manner. Whether OAZ has a more general role in protein degradation and has other targets is unknown. In support of a functional relationship between Guf and Vn, the results of genetic tests suggest that guf negatively regulates Vn/EGFR activity. Furthermore, I found genetic evidence that Vn may be degraded by 26S proteasome, and that Guf is involved in 26S mediated protein degradation. These data raise the possibility that the binding of Guf to Vn might be involved in targeting Vn to be degraded by the 26S proteasome. Further experiments to localize the proteins in cells and to investigate the mechanism of Vn degradation will be critical for examining this hypothesis.
Committee
Amanda Simcox (Advisor)
Pages
189 p.
Subject Headings
Biology, Genetics
Keywords
vein
;
Drosophila
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Citations
Wang, S.-H. (2003).
Regulation of vein, an activating ligand of the drosophila EGF receptor
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054165285
APA Style (7th edition)
Wang, Shu-Huei.
Regulation of vein, an activating ligand of the drosophila EGF receptor.
2003. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1054165285.
MLA Style (8th edition)
Wang, Shu-Huei. "Regulation of vein, an activating ligand of the drosophila EGF receptor." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054165285
Chicago Manual of Style (17th edition)
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Document number:
osu1054165285
Download Count:
940
Copyright Info
© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.