| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 47, 45122-45128, November 22, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Human cytomegalovirus encodes the G
protein-coupled chemokine receptor homologue US28 that binds several CC
chemokines and sequesters extracellular chemokines from the environment
of infected cells. Mechanistically, it has been shown that US28
undergoes rapid constitutive receptor endocytosis and recycling.
Monoclonal antibodies were raised that allowed the characterization of
a ligand-independent phosphorylation and low surface expression of the
US28 receptor in transiently transfected HEK293A cells. Phosphoamino
acid analysis defined C-terminal serine and threonine residues as
phospho-acceptor sites for constitutive receptor phosphorylation. Coexpression of G protein-coupled receptor kinase-2 and US28 enhanced ligand-independent receptor phosphorylation. C-terminal serine to
alanine mutagenesis of US28 resulted in a decreased phosphorylation rate that correlated with enhanced surface expression. Maximal surface
expression was detected when all C-terminal serines were substituted.
Exchange of all C-terminal serines also significantly reduced
receptor endocytosis. Thus, constitutive US28 phosphorylation regulates
receptor endocytosis and receptor surface display and may thereby
provide a pathogenic mechanism for a potential decoy function of the
virally encoded receptor.
Surface Expression and Endocytosis of the Human
Cytomegalovirus-encoded Chemokine Receptor US28 Is Regulated by
Agonist-independent Phosphorylation*
,§¶,§¶,
,, and**
Max-Delbrück-Center for Molecular
Medicine, Department of Tumorgenetics and Immunogenetics and
Department of Hematology, Oncology, and Tumorimmunology, 13092 Berlin,
§ Robert-Rössle-Klinik, Department of Hematology,
Oncology, and Tumorimmunology, Universitätsklinikum Charite,
13125 Berlin, and Department of Immunology,
University of Göttingen, Göttingen 37075, Germany
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. P. M. Stropes and W. E. Miller Functional analysis of human cytomegalovirus pUS28 mutants in infected cells J. Gen. Virol., January 1, 2008; 89(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chernajovsky, L. Layward, and N. Lemoine Fighting cancer with oncolytic viruses BMJ, January 21, 2006; 332(7534): 170 - 172. [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Paulsen, M. M. Rosenkilde, J. Eugen-Olsen, and T. N. Kledal Epstein-Barr Virus-Encoded BILF1 Is a Constitutively Active G Protein-Coupled Receptor J. Virol., January 1, 2005; 79(1): 536 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Morris, R. R. Price, M. P. Smith, B. Lei, and D. A. Schwinn Cellular Trafficking of Human {alpha}1a-Adrenergic Receptors Is Continuous and Primarily Agonist-Independent Mol. Pharmacol., October 1, 2004; 66(4): 843 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Galliera, V. R. Jala, J. O. Trent, R. Bonecchi, P. Signorelli, R. J. Lefkowitz, A. Mantovani, M. Locati, and B. Haribabu {beta}-Arrestin-dependent Constitutive Internalization of the Human Chemokine Decoy Receptor D6 J. Biol. Chem., June 11, 2004; 279(24): 25590 - 25597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Weber, E. Blair, C. V. Simpson, M. O'Hara, P. E. Blackburn, A. Rot, G. J. Graham, and R. J.B. Nibbs The Chemokine Receptor D6 Constitutively Traffics to and from the Cell Surface to Internalize and Degrade Chemokines Mol. Biol. Cell, May 1, 2004; 15(5): 2492 - 2508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Miller, D. A. Houtz, C. D. Nelson, P. E. Kolattukudy, and R. J. Lefkowitz G-protein-coupled Receptor (GPCR) Kinase Phosphorylation and {beta}-Arrestin Recruitment Regulate the Constitutive Signaling Activity of the Human Cytomegalovirus US28 GPCR J. Biol. Chem., June 6, 2003; 278(24): 21663 - 21671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Waldhoer, P. Casarosa, M. M. Rosenkilde, M. J. Smit, R. Leurs, J. L. Whistler, and T. W. Schwartz The Carboxyl Terminus of Human Cytomegalovirus-encoded 7 Transmembrane Receptor US28 Camouflages Agonism by Mediating Constitutive Endocytosis J. Biol. Chem., May 23, 2003; 278(21): 19473 - 19482. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
