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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gilmore, Rodney C. Watson, Michael J. Archer, Christopher B. Tarran, Robert Sheridan, John T. |
| Description | Author Affiliation: Sheridan JT ( From the Department of Cell and Molecular Physiology and.) |
| Abstract | Sex plays a significant role in the development of lung diseases including asthma, cancer, chronic bronchitis, and cystic fibrosis. In cystic fibrosis, 17ß-estradiol (E2) may inhibit store-operated Ca(2+) entry (SOCE) to impinge upon airway secretions, leaving females at greater risk of contracting lung infections. Stromal interaction molecule 1 (STIM1)-mediated SOCE is essential for cell homeostasis and regulates numerous processes including cell proliferation, smooth muscle contraction, and secretion. E2 can signal nongenomically to modulate Ca(2+) signaling, but little is known of the underlying mechanisms. We found that E2 exposure inhibited STIM1 translocation in airway epithelia, preventing SOCE. This correlated with a decrease in STIM1-STIM1 FRET and STIM1 mobility in E2-exposed HEK293T cells co-expressing estrogen receptor . We also examined the role of STIM1 phosphorylation in E2-mediated inhibition of STIM1 mobility. STIM1 is basally phosphorylated at serine 575, which is required for SOCE. Exposure to E2 significantly decreased STIM1 serine phosphorylation. Mutating serine 575 to an alanine blocked STIM1 phosphorylation, reduced basal STIM1 mobility, and rendered STIM1 insensitive to E2. These data indicate that E2 can signal nongenomically by inhibiting basal phosphorylation of STIM1, leading to a reduction in SOCE. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 47 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-11-22 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Signaling Drug Effects Calcium Metabolism Estradiol Pharmacology Lung Diseases Membrane Proteins Neoplasm Proteins Amino Acid Substitution Genetics Cell Line Cell Proliferation Estrogen Receptor Alpha Pathology Mutation, Missense Phosphorylation Clinical Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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