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Analysis of newly identified protease‐activated receptor‐2‐interacting proteins and their role in receptor signalling in the control of gene expression and receptor recycling
Author(s) -
Reiser Georg,
Wang Yingfei,
Luo Weibo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a983-d
Subject(s) - microbiology and biotechnology , signal transduction , receptor , endocytosis , intracellular , g protein coupled receptor , biology , endosome , golgi apparatus , 5 ht5a receptor , g protein , biochemistry , endoplasmic reticulum
For protease‐activated receptor‐2 (PAR‐2), a G protein‐coupled receptor for trypsin, intracellular signal transductions are hardly understood. We identified interacting partners of human PAR‐2. For Jun activation domain‐binding protein 1 (Jab1), the interaction was confirmed in vitro and in vivo. Multiple intracellular domains of PAR‐2 are required for interaction. Agonist stimulation of PAR‐2 disrupted the interaction and induced redistribution of Jab1, which could be prevented by inhibition of receptor endocytosis. Furthermore, Jab1 mediated PAR‐2‐induced c‐Jun activation, which was followed by increased activation of AP‐1. Thus, Jab1 is an important effector that mediates a novel signal transduction pathway for PAR‐2‐dependent gene expression. We also characterized coated vesicle membrane proteins of p24 family as PAR‐2‐interacting protein. p24A members are colocalized with intracellular PAR‐2 at Golgi stores. Activation of PAR‐2 resulted in protein dissociation of p24A from PAR‐2 at a time, when the intracellular receptor was sorted to the plasma membrane for resensitization. p24A members trap PAR‐2 at the Golgi apparatus, which is essential for the intracellular PAR‐2 pool formation. The interaction also assists PAR‐2 receptor resensitization and sorting to the plasma membrane. This might explain the molecular mechanism underlying post‐Golgi transport of GPCRs to the plasma membrane. (DFG)