Related Experiment Video
Updated: Dec 7, 2025

Two Methods for Establishing Primary Human Endometrial Stromal Cells from Hysterectomy Specimens
Published on: May 23, 2014
Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal
So Young Lee1, Yun Young Lee1,2, Joong-Sub Choi3
1Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.
Abstract:
Decidualization of the endometrial stroma is an essential differentiation process for embryo implantation and maintenance of pregnancy. We previously reported that protein phosphatase 2A (PP2A) acts as a key mediator during cAMP-induced decidualization of human endometrial stromal cells (hESCs). However, the mechanism underlying its activation has remained obscure in hESCs. In the present study, we aimed to reveal the mechanism that induces the nitration of PP2A catalytic subunit (PP2Ac) during cAMP-induced decidualization of hESCs. First, cAMP-induced PP2Ac nitration was significantly repressed using L-NAME, an inhibitor of nitric oxide synthase (NOS). Among several NOS isoforms, only inducible NOS (iNOS) was highly expressed in hESCs, indicating that iNOS directly induces the nitration of PP2Ac. Second, cAMP-induced iNOS expression and PP2Ac nitration were decreased by treatment with TSA, an inhibitor of histone deacetylase 5 (HDAC5). cAMP-induced phosphorylation of CaMKII and HDAC5 was suppressed by treatment with U73122 (an inhibitor of phospholipase C) or transfection of PLCε siRNA. Finally, small G protein Rap1 and its guanine nucleotide exchange factor Epac1 were found to be involved in cAMP-induced PP2A activation. Taken together, our results suggest that PP2Ac nitration during cAMP-induced decidualization of hESCs is induced through the Epac1-Rap1-PLCε-CaMKII-HDAC5-iNOS signaling pathway.
Related Concept Videos
Nitric Oxide Signaling Pathway
cAMP-dependent Protein Kinase Pathways
IP3/DAG Signaling Pathway
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Amplifying Signals via Enzymatic Cascade

