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Identification of Functional Glycosylation of ADAMTSL2

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dc.contributor.advisor Holdener, Bernadette C, Brown, Deborah A en_US
dc.contributor.author Taibi, Andrew en_US
dc.contributor.other Department of Biochemistry and Cell Biology en_US
dc.date.accessioned 2013-05-22T17:35:41Z
dc.date.accessioned 2015-04-24T14:47:32Z
dc.date.available 2013-05-22T17:35:41Z
dc.date.available 2015-04-24T14:47:32Z
dc.date.issued 2012-12-01 en_US
dc.identifier Taibi_grad.sunysb_0771M_11222 en_US
dc.identifier.uri http://hdl.handle.net/1951/59884 en_US
dc.identifier.uri http://hdl.handle.net/11401/71429 en_US
dc.description 39 pg. en_US
dc.description.abstract ADAMTSL2 has been shown to play a role in regulation of Transforming Growth Factor β (TGFβ) signaling through binding Latent TGFβ Binding Protein 1 (LTBP1) and Fibrillin 1 (FBN1) in the extracellular matrix. A genetic screen revealed mutations to Adamtsl2 cause a rare growth disorder called Geleophysic Dysplasia (GD). Multiple GD mutations fall within ADAMTSL2's seven Thrombospondin Type 1 Repeats (TSRs). TSRs often undergo a form of glycosylation called O-fucosylation. The addition of a fucose sugar to TSRs has been shown to be a necessary process in the secretion of related proteins. Among several mutations to ADAMTSL2 within TSRs which cause GD, two are predicted to interfere with O-fucosylation. In this study we reproduced these two GD-associated mutations as well as three additional mutations predicted to interfere with glycosylation in an unusual O-fucosylation site on TSR6. The predicted O-fucose site on TSR6 actually overlaps with a predicted site of N-glycosylation. Our three TSR6 mutant constructs were designed to both address which type of modification is occurring as well as its importance in protein secretion. We utilized expression constructs incorporating these mutations in parallel transactions to assay their effect on protein secretion in 293T cells. We predict that mutations predicted to affect O-fucosylation will impair secretion, while our mutation interfering with N-glycosylation will not. In this way we hope to provide a functional link between mutations to ADAMTSL2 and GD. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biology--Biochemistry en_US
dc.title Identification of Functional Glycosylation of ADAMTSL2 en_US
dc.type Thesis en_US
dc.mimetype Application/PDF en_US


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