Dalhousie Repository
The effect of phosphorylation on oxysterol-binding protein (OSBP) sterol binding activity
DalSpace/Manakin Repository
JavaScript is disabled for your browser. Some features of this site may not work without it.
| 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 5S5E had increased cholesterol binding and extraction, and decreased cholesterol transfer to liposomes compared to OSBP. OSBP 5S5E 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 |
