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Agonist‐induced internalization and mitogen‐activated protein kinase activation of the human prostaglandin EP4 receptor
Author(s) -
Desai Snehal,
Ashby Barrie
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02640-0
Subject(s) - internalization , chemistry , agonist , protein kinase a , prostaglandin e2 receptor , microbiology and biotechnology , receptor , mitogen activated protein kinase , prostaglandin , kinase , biochemistry , biology
We examined the pathway of prostaglandin E 2 (PGE 2 )‐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. PGE 2 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.