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The effect of phosphorylation on oxysterol-binding protein (OSBP) sterol binding activity

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dc.contributor.author Robinson, Carolyn-Ann
dc.date.accessioned 2012-09-11T11:38:26Z
dc.date.available 2012-09-11T11:38:26Z
dc.date.issued 2012-09-11
dc.identifier.uri http://hdl.handle.net/10222/15489
dc.description.abstract Oxysterol binding protein (OSBP) binds 25-hydroxycholesterol (25OH) and cholesterol, which regulates PH and FFAT domain interaction with the Golgi apparatus and endoplasmic reticulum, respectively. Adjacent to these domains is a phosphorylated serine-rich motif (SRM, T379, S381, S384, S387, S388, S391) that we hypothesize controls sterol transport by OSBP. To test this, OSBP dephospho-mimics or phospho-mimics were expressed in CHO cells. Western blot analysis showed that the S381 is phosphorylated by PKA and is required for phosphorylation of down-stream serine residues. When expressed in OSBP-null CHO cells, there was no difference in the localization of the OSBP mutants, and all mutants restored SM synthesis in response to 25OH. Recombinant OSBP 5S?5E had increased cholesterol binding and extraction, and decreased cholesterol transfer to liposomes compared to OSBP. OSBP 5S?5E also bound VAP more efficiently. A model is proposed wherein SRM phosphorylation facilitates VAP association with the ER and increases cholesterol extraction. en_US
dc.language.iso en en_US
dc.subject cholesterol en_US
dc.subject oxysterol en_US
dc.subject sterol transport en_US
dc.subject phosphorylation en_US
dc.title The effect of phosphorylation on oxysterol-binding protein (OSBP) sterol binding activity en_US
dc.date.defence 2011-05-10
dc.contributor.department Department of Biochemistry & Molecular Biology en_US
dc.contributor.degree Master of Science en_US
dc.contributor.external-examiner N/A en_US
dc.contributor.graduate-coordinator John Archibald en_US
dc.contributor.thesis-reader Barbara Karten en_US
dc.contributor.thesis-reader Roger McLeod en_US
dc.contributor.thesis-reader Aarnoud van der Spoel en_US
dc.contributor.thesis-supervisor Neale Ridgway en_US
dc.contributor.ethics-approval Not Applicable en_US
dc.contributor.manuscripts Not Applicable en_US
dc.contributor.copyright-release Not Applicable en_US

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