Agonist‐induced internalization and mitogen‐activated protein kinase activation of the human prostaglandin EP4 receptor

FEBS Letters

Desai, Snehal¹  Ashby, Barrie¹ 

[1] Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA

关键词: Prostaglandin E2;    EP4 receptor;    Internalization;    Mitogen-activated protein kinase;   

DOI  :  10.1016/S0014-5793(01)02640-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We examined the pathway of prostaglandin E₂ (PGE₂)-induced internalization of the prostaglandin EP4 receptor in HEK 293 cells. Co-expression of dominant negative β-arrestin (319–418) or dynamin I (K44A) with the EP4 receptor reduced internalization. The activated receptor co-localized with GFP-arrestin 2 and GFP-arrestin 3, confirming the requirement for β-arrestins in internalization. Inhibition of clathrin-coated vesicle-mediated internalization resulted in inhibition of sequestration, whereas inhibition of caveola-mediated internalization had no effect. PGE₂ stimulation of the EP4 receptor resulted in rapid mitogen-activated protein (MAP) kinase activation. Examination of an internalization-resistant mutant and co-expression of mutant accessory proteins with EP4 revealed that MAP kinase activation proceeds independently of internalization.

【 授权许可】

Unknown