期刊
CELLULAR SIGNALLING
卷 25, 期 12, 页码 2362-2373出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.07.020
关键词
MC3T3-E1 cells; l alpha,25(OH)(2)D-3; Rapid responses; Pdia3; VDR; Caveolin-1
类别
资金
- Price Gilbert, Jr. Foundation
- Children's Healthcare of Atlanta
1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)(2)D-3) regulates osteoblasts through genomic and rapid membrane-mediated responses. Here we examined the interaction of protein disulfide isomerase family A. member 3 (Pdia3) and the traditional vitamin D receptor (VDR) in plasma membrane-associated responses to l alpha,25(OH)(2)D-3. We found that Pdia3 co-localized with VDR and the caveolae scaffolding protein, caveolin-1 on the surface of MC3T3-E1 osteoblasts. Immunoprecipitation showed that both Pdia3 and VDR interacted with caveolin-1. Pdia3 further interacted with phospholipase A2 activating protein (PLAA), whereas VDR interacted with c-Src. l alpha,25(OH)(2)D-3 changed the interactions and transport of the two receptors and rapidly activated phospholipase A2 (PLA2) and c-Src. Silencing either receptor or caveolin-1 inhibited both PLA2 and c-Src, indicating that the two receptors function interdependently. These two receptor dependent rapid responses to 1 alpha,25(OH)(2)D-3 regulated gene expression, proliferation and apoptosis of MC3T3-E1 cells. These data demonstrate the importance of both receptors and caveolin-1 in mediating membrane responses to 1 alpha,25(OH)(2)D-3 and subsequently regulating osteoblast biology. (C) 2013 Elsevier Inc. All rights reserved.
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