on November 11, 2004
Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150662.51436.14
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Submitted on August 10, 2004
Accepted on November 1, 2004
Regulation of Transport of the Angiotensin AT2 Receptor by a Novel Membrane-Associated Golgi Protein
Christoph J. Wruck ;
From the Institute of Pharmacology (C.J.W.) and the First Department of Medicine (M.L.K.), University Hospital Schleswig-Holstein, Campus Kiel; the Institute of Anatomy (T.P.), University of Kiel; the Center for Cardiovascular Research/Institute of Pharmacology and Toxicology (H.K., M.M., H.F.-K., J.S., T.U.), Charité-University Medicine Berlin; and the Institute for Arteriosclerosis Research at the University of Muenster (M.S.), Germany.
* To whom correspondence should be addressed. E-mail: thomas.unger{at}charite.de.
Objective--Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination of processes including protein folding, posttranslational modifications, and transport through distinct cellular compartments. Little is known concerning the regulation of G protein-coupled receptor transport from the endoplasmic reticulum to the cell surface.
Methods and Results--Here we show that the cytoplasmatic carboxy-terminal of the angiotensin AT2 receptor (AT2R) acts independently as an endoplasmic reticulum-export signal. Using a yeast two-hybrid system, we identified a Golgi membrane-associated protein termed ATBP50 (for AT2R binding protein of 50 kDa) that binds to this motif. We also cloned ATBP60 and ATBP135 encoded by the same gene as ATBP50 that mapped to chromosomes 8p21.3. Downregulation of ATBP50 using siRNA leads to retention of AT2R in inner compartments, reduced cell surface expression, and decreased antiproliferative effects of the receptor.
Conclusion--Our results indicate that ATBP50 regulates the transport of the AT2R to cell membrane by binding to a specific signal within its cytoplasmic carboxy-terminal and thereby enabling the antiproliferative effects of the receptor.
Key words: AT2 receptor • ATBP50 • receptor transport • Golgi proteins • ERK1/2
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