AKAP95-mediated nuclear anchoring of PKA mediates cortisol-induced PTGS2 expression in human amnion fibroblasts

• DOI: 10.1126/scisignal.aac6160
• Publication Date: 2017-11-21T19:25:41Z
• Authors: Jiangwen Lu; Wangsheng Wang; Yabing Mi; Chuyue Zhang; Hao Ying; Luyao Wang; Yawei Wang; Leslie Myatt; Kang Sun
• Keywords: Amnion; Cyclic adenosine monophosphate

Phosphorylation of the transcription factors cyclic adenosine monophosphate response element-binding protein (CREB) and signal transducer activator 3 (STAT3) by kinase A (PKA) is required for cortisol-induced production cyclooxygenase-2 (COX-2) prostaglandin E2 (PGE2) in human amnion fibroblasts, which critically mediates parturition (labor). We found that PKA was confined nucleus A-kinase-anchoring 95 (AKAP95) fibroblasts this localization key to expression PTGS2, gene encoding COX-2. Cortisol increased abundance nuclear stimulating AKAP95. Knockdown AKAP95 not only reduced amounts phosphorylated CREB but also attenuated induction PTGS2 primary treated with cortisol, whereas phosphorylation STAT3 cortisol affected. The abundances AKAP95, CREB, COX-2 were markedly tissue after labor compared those tissues from cesarean sections without labor. These results highlight an essential role anchored consequent may be important parturition.