Mucin-type O-linked glycosylation is a post-translational modification in which proteins are highly decorated by carbohydrate chains. These oligosaccharides serve as mediators of information between cells and are crucial for cell-cell communication. Changes in expression patterns of mucin-type O-linked glycoproteins is believed to contribute to both the invasive and metastatic properties of tumor cells. The biosynthesis of mucin is initiated by a family of enzymes collectively known as the ppGaINAcTs. Characterization of ppGaINAcT substrate specificity and the properties conferring this specificity for each individual isoform has been a difficult task. We propose to use a unique combination of chemistry and molecular biology to facilitate the further understanding of this enzyme family in a stepwise process.
Aim 1. Synthesize and systematically analyze a library of glycopeptides to determine the substrate preference of each ppGaINAcT isoform.
Aim 2. Create chimeric enzymes to determine what parts of the protein are responsible for conferring specificity. Finally, Aim 3. To correlate the specificity patterns for various isoforms observed in vitro with substrate preference within cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM073442-01
Application #
6884201
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Lograsso, Philip
Project Start
2005-03-01
Project End
2008-02-29
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
1
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704