ArticleThe Journal of biological chemistry2011
Ras/mitogen-activated protein kinase (MAPK) signaling modulates protein stability and cell surface expression of scavenger receptor SR-BI.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease.Biomedicines · 2023Review
- The potential role of scavenger receptor B type I (SR-BI) in SARS-CoV-2 infection.Immunity, inflammation and disease · 2023Review
- Efficacy and underlying mechanisms of berberine against lipid metabolic diseases: a review.Frontiers in pharmacology · 2023Review
- Recombinant Humanized IgG1 Antibody Promotes Reverse Cholesterol Transport through FcRn-ERK1/2-PPARα Pathway in Hepatocytes.International journal of molecular sciences · 2022Article
- HDL and Scavenger Receptor Class B Type I (SRBI).Advances in experimental medicine and biology · 2022Review
- Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet.BMC genomics · 2021Article
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- Mechanisms of Niemann-Pick type C1 Like 1 protein degradation in intestinal epithelial cells.American journal of physiology. Cell physiology · 2019Article
- CC-Chemokine Ligand 2 (CCL2) Suppresses High Density Lipoprotein (HDL) Internalization and Cholesterol Efflux via CC-Chemokine Receptor 2 (CCR2) Induction and p42/44 Mitogen-activated Protein Kinase (MAPK) Activation in Human Endothelial Cells.The Journal of biological chemistry · 2016Article
- SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer.Frontiers in pharmacology · 2016Review
- Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1.Biochimica et biophysica acta · 2015Article
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Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitogen-activated protein kinase (MAPK) Erk1/2 has been implicated to modulate the activity of nuclear receptors, including peroxisome proliferator activator receptors (PPARs) and liver X receptor, to alter the ability of cells to export cholesterol. Here, we investigated if the Ras-Raf-Mek-Erk1/2 signaling cascade could affect reverse cholesterol transport via modulation of scavenger receptor class BI (SR-BI) levels. We demonstrate that in Chinese hamster ovary (CHO) and human embryonic kidney (HEK293) cells, Mek1/2 inhibition reduces PPARα-inducible SR-BI protein expression and activity, as judged by reduced efflux onto high density lipoprotein (HDL). Ectopic expression of constitutively active H-Ras and Mek1 increases SR-BI protein levels, which correlates with elevated PPARα Ser-21 phosphorylation and increased cholesterol efflux. In contrast, SR-BI levels are insensitive to Mek1/2 inhibitors in PPARα-depleted cells. Most strikingly, Mek1/2 inhibition promotes SR-BI degradation in SR-BI-overexpressing CHO cells and human HuH7 hepatocytes, which is associated with reduced uptake of radiolabeled and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyane-labeled HDL. Loss of Mek1/2 kinase activity reduces SR-BI expression in the presence of bafilomycin, an inhibitor of lysosomal degradation, indicating down-regulation of SR-BI via proteasomal pathways. In conclusion, Mek1/2 inhibition enhances the PPARα-dependent degradation of SR-BI in hepatocytes.
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Registered trials
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