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PMID:21937726
| Citation |
Kim, KH, Toomre, D and Bender, JR (2011) Splice isoform estrogen receptors as integral transmembrane proteins. Mol. Biol. Cell 22:4415-23 |
|---|---|
| Abstract |
In addition to enhancing or repressing transcription, steroid hormone receptors rapidly transduce kinase activation signals. On ligand engagement, an N-terminus-truncated splice isoform of estrogen receptor (ER) α, ER46, triggers membrane-initiated signals, resulting in endothelial nitric oxide synthase (eNOS) activation and endothelial NO production. The orientation of ER46 at the plasma membrane is incompletely defined. With the use of ecliptic pHluorin-fused ER46, total internal reflection fluorescence microscopy in live human endothelial cells illustrates that ER46 can topologically conform to a type I transmembrane protein structure. Mutation of isoleucine-386 at the center of ER46's transmembrane hydrophobic core prevents membrane spanning, obscures the N-terminal ectodomain, and effects a marked reduction in membrane-impermeant estrogen binding with diminished rapid eNOS activation and NO production, despite maintained genomic induction of an estrogen response element-luciferase reporter. Thus there exist pools of transmembrane steroid hormone receptors that are efficient signaling molecules and potential novel therapeutic targets. |
| Links |
PubMed PMC3216666 Online version:10.1091/mbc.E11-05-0416 |
| Keywords |
Cell Line; Cell Membrane/metabolism; Endothelial Cells/metabolism; Enzyme Activation; Estrogen Receptor alpha/chemistry; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/metabolism; Green Fluorescent Proteins; Humans; Membrane Proteins/metabolism; Mutation; Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type III/metabolism; Protein Conformation; Protein Isoforms/metabolism; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/metabolism; Signal Transduction |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0051000: positive regulation of nitric-oxide synthase activity |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0045429: positive regulation of nitric oxide biosynthetic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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