| First Author | Shindo S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e84462 |
| PubMed ID | 24386386 | Mgi Jnum | J:209841 |
| Mgi Id | MGI:5568812 | Doi | 10.1371/journal.pone.0084462 |
| Citation | Shindo S, et al. (2013) Serine 216 phosphorylation of estrogen receptor alpha in neutrophils: migration and infiltration into the mouse uterus. PLoS One 8(12):e84462 |
| abstractText | BACKGROUND: Whereas estrogen receptors are present in immune cells, it is not known if they are phosphorylated to regulate immune cell functions. Here we determined the phosphorylation status of estrogen receptor alpha (ERalpha) at residue serine 216 in mouse neutrophils and examined its role in migration and infiltration. Serine 216 is the conserved phosphorylation site within the DNA binding domains found in the majority of nuclear receptors. METHODOLOGY/PRINCIPAL FINDINGS: A phospho-peptide antibody specific to phosphorylated serine 216 and ERalpha KO mice were utilized in immunohistochemistry, double immuno-staining or Western blot to detect phosphorylation of ERalpha in peripheral blood as well as infiltrating neutrophils in the mouse uterus. Transwell assays were performed to examine migration of neutrophils. An anti-Ly6G antibody identified neutrophils. About 20% of neutrophils expressed phosphorylated ERalpha at serine 216 in peripheral white blood cells (WBC) from C3H/HeNCrIBR females. Phosphorylation was additively segregated between C3H/HeNCrIBR and C57BL/6 females. Only neutrophils that expressed phosphorylated ERalpha migrated in Transwell assays as well as infiltrated the mouse uterus during normal estrous cycles. CONCLUSIONS/SIGNIFICANCE: ERalpha was phosphorylated at serine 216 in about 20% of mouse peripheral blood neutrophils. Only those that express phosphorylated ERalpha migrate and infiltrate the mouse uterus. This phosphorylation was the first to be characterized in endogenous ERalpha found in normal tissues and cells. Phosphorylated ERalpha may have opened a novel research direction for biological roles of phosphorylation in ERalpha actions and can be developed as a drug target for treatment of immune-related diseases. |
