|
Originally published In Press as doi:10.1074/jbc.M009275200 on March 9, 2001
J. Biol. Chem., Vol. 276, Issue 21, 18066-18074, May 25, 2001
Casein Kinase II Sites in the Intracellular C-terminal Domain of
the Thyrotropin-releasing Hormone Receptor and Chimeric
Gonadotropin-releasing Hormone Receptors Contribute to
-Arrestin-dependent Internalization*
Aylin C.
Hanyaloglu §¶ ,
Milka
Vrecl**,
Karen M.
Kroeger ,
Lauren E. C.
Miles ¶,
Hongwei
Qian ,
Walter G.
Thomas §§, and
Karin A.
Eidne §¶¶¶
From the 7TM Receptor Laboratory, Western Australian
Institute for Medical Research, § Keogh Institute for
Medical Research, Sir Charles Gairdner Hospital, and ¶ Animal
Sciences, University of Western Australia, Perth, Western Australia
6009, Australia, ** Veterinary Faculty, University of Ljubljana, 1000 Ljubljana Slovenia, and  Baker
Medical Research Institute, Melbourne 8008, Australia
We have previously shown that the mammalian
gonadotropin-releasing hormone receptor (GnRHR), a unique
G-protein-coupled receptor (GPCR) lacking an intracellular carboxyl
tail (C-tail), does not follow a -arrestin-dependent
internalization pathway. However, internalization of a chimeric GnRHR
with the thyrotropin-releasing hormone receptor (TRHR) C-tail does
utilize -arrestin. Here, we have investigated the sites within the
intracellular C-tail domain that are important for conferring
-arrestin-dependent internalization. In contrast to the
chimeric GnRHR with a TRHR C-tail, a chimeric GnRHR with the catfish
GnRHR C-tail is not -arrestin-dependent. Sequence
comparisons between these chimeric receptors show three consensus
phosphorylation sites for casein kinase II (CKII) in the TRHR C-tail
but none in the catfish GnRHR C-tail. We thus investigated a role for
CKII sites in determining GPCR internalization via -arrestin.
Sequential introduction of three CKII sites into the chimera with the
catfish C-tail (H354D,A366E,G371D) resulted in a change in the
pattern of receptor phosphorylation and -arrestin-dependence, which
only occurred when all three sites were introduced. Conversely,
mutation of the putative CKII sites (T365A,T371A,S383A) in the C-tail
of a -arrestin-sensitive GPCR, the TRHR, resulted in decreased
receptor phosphorylation and a loss of -arrestin-dependence.
Mutation of all three CKII sites was necessary before a loss of
-arrestin-dependence was observed. Visualization of -arrestin/GFP
redistribution confirmed a loss or gain of -arrestin sensitivity for
receptor mutants. Internalization of receptors without C-tail CKII
sites was promoted by a phosphorylation-independent -arrestin mutant
(R169E), suggesting that these receptors do not contain the necessary
phosphorylation sites required for -arrestin-dependent
internalization. Apigenin, a specific CKII inhibitor, blocked the
increase in receptor internalization by -arrestin, thus providing
further support for the involvement of CKII. This study presents
evidence of a novel role for C-tail CKII consensus sites in targeting
these GPCRs to the -arrestin-dependent pathway.
*
This work was supported by grants from the National Health
and Medical Research Council of Australia and the Raine Foundation (to
K. A. E).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.
Recipient of a Keogh Institute of Medical Research
postgraduate scholarship.
§§
Supported in part by a Block grant from the National Health and
Medical Research Council of Australia to the Baker Medical Research Institute.
¶¶
To whom correspondence should be addressed: WAIMR, B
Block, Sir Charles Gairdner Hospital, Hospital Ave., Nedlands, Perth, WA 6009, Australia. Tel.: 61 08 9346 1980; Fax: 61 08 9346 1818; E-mail: keidne@waimr.uwa.edu.au.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. Vrecl, P. K. Norregaard, D. L.C. Almholt, L. Elster, A. Pogacnik, and A. Heding
{beta}-Arrestin-Based Bret2 Screening Assay for the "Non"-{beta}-Arrestin Binding CB1 Receptor
J Biomol Screen,
April 1, 2009;
14(4):
371 - 380.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Tello, S. Wu, J. E. Rivier, and N. M. Sherwood
Four functional GnRH receptors in zebrafish: analysis of structure, signaling, synteny and phylogeny
Integr. Comp. Biol.,
November 1, 2008;
48(5):
570 - 587.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Maurice, A. M. Daulat, C. Broussard, J. Mozo, G. Clary, F. Hotellier, P. Chafey, J.-L. Guillaume, G. Ferry, J. A. Boutin, et al.
A Generic Approach for the Purification of Signaling Complexes That Specifically Interact with the Carboxyl-terminal Domain of G Protein-coupled Receptors
Mol. Cell. Proteomics,
August 1, 2008;
7(8):
1556 - 1569.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Pawson, E. Faccenda, S. Maudsley, Z.-L. Lu, Z. Naor, and R. P. Millar
Mammalian Type I Gonadotropin-Releasing Hormone Receptors Undergo Slow, Constitutive, Agonist-Independent Internalization
Endocrinology,
March 1, 2008;
149(3):
1415 - 1422.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Hubert, S. Paris, J.-P. Piret, N. Ninane, M. Raes, and C. Michiels
Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level
J. Cell Sci.,
August 15, 2006;
119(16):
3351 - 3362.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Navratil, T. A. Farmerie, J. Bogerd, T. M. Nett, and C. M. Clay
Differential Impact of Intracellular Carboxyl Terminal Domains on Lipid Raft Localization of the Murine Gonadotropin-Releasing Hormone Receptor
Biol Reprod,
May 1, 2006;
74(5):
788 - 797.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. W. Jones and P. M. Hinkle
{beta}-Arrestin Mediates Desensitization and Internalization but Does Not Affect Dephosphorylation of the Thyrotropin-releasing Hormone Receptor
J. Biol. Chem.,
November 18, 2005;
280(46):
38346 - 38354.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Y. Oh, J. A. Song, J. S. Moon, M. J. Moon, J. I. Kim, K. Kim, H. B. Kwon, and J. Y. Seong
Membrane-Proximal Region of the Carboxyl Terminus of the Gonadotropin-Releasing Hormone Receptor (GnRHR) Confers Differential Signal Transduction between Mammalian and Nonmammalian GnRHRs
Mol. Endocrinol.,
March 1, 2005;
19(3):
722 - 731.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Ronacher, N. Matsiliza, N. Nkwanyana, A. J. Pawson, T. Adam, C. A. Flanagan, R. P. Millar, and A. A. Katz
Serine Residues 338 and 339 in the Carboxyl-Terminal Tail of the Type II Gonadotropin-Releasing Hormone Receptor Are Critical for {beta}-Arrestin-Independent Internalization
Endocrinology,
October 1, 2004;
145(10):
4480 - 4488.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. J. Caunt, J. N. Hislop, E. Kelly, A.-L. Matharu, L. D. Green, K. R. Sedgley, A. R. Finch, and C. A. McArdle
Regulation of Gonadotropin-Releasing Hormone Receptors by Protein Kinase C: Inside Out Signalling and Evidence for Multiple Active Conformations
Endocrinology,
August 1, 2004;
145(8):
3594 - 3602.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Cook and P. M. Hinkle
Fate of Internalized Thyrotropin-Releasing Hormone Receptors Monitored with a Timer Fusion Protein
Endocrinology,
July 1, 2004;
145(7):
3095 - 3100.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Yin, S. Gavi, H.-y. Wang, and C. C. Malbon
Probing Receptor Structure/Function with Chimeric G-Protein-Coupled Receptors
Mol. Pharmacol.,
June 1, 2004;
65(6):
1323 - 1332.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Pawson, S. R. Maudsley, J. Lopes, A. A. Katz, Y.-M. Sun, J. S. Davidson, and R. P. Millar
Multiple Determinants for Rapid Agonist-Induced Internalization of a Nonmammalian Gonadotropin-Releasing Hormone Receptor: A Putative Palmitoylation Site and Threonine Doublet within the Carboxyl-Terminal Tail Are Critical
Endocrinology,
September 1, 2003;
144(9):
3860 - 3871.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Gray, A. Bhatnagar, V. V. Gurevich, and B. L. Roth
The Interaction of a Constitutively Active Arrestin with the Arrestin-Insensitive 5-HT2A Receptor Induces Agonist-Independent Internalization
Mol. Pharmacol.,
May 1, 2003;
63(5):
961 - 972.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. MEGGIO and L. A. PINNA
One-thousand-and-one substrates of protein kinase CK2?
FASEB J,
March 1, 2003;
17(3):
349 - 368.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. C. Hanyaloglu, R. M. Seeber, T. A. Kohout, R. J. Lefkowitz, and K. A. Eidne
Homo- and Hetero-oligomerization of Thyrotropin-releasing Hormone (TRH) Receptor Subtypes. DIFFERENTIAL REGULATION OF beta -ARRESTINS 1 AND 2
J. Biol. Chem.,
December 20, 2002;
277(52):
50422 - 50430.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Gaudreau, C. Le Gouill, M.-H. Venne, J. Stankova, and M. Rola-Pleszczynski
Threonine 308 within a Putative Casein Kinase 2 Site of the Cytoplasmic Tail of Leukotriene B4 Receptor (BLT1) Is Crucial for Ligand-induced, G-protein-coupled Receptor-specific Kinase 6-mediated Desensitization
J. Biol. Chem.,
August 23, 2002;
277(35):
31567 - 31576.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.-C. Zhu, L. B. Cook, and P. M. Hinkle
Dimerization and Phosphorylation of Thyrotropin-releasing Hormone Receptors Are Modulated by Agonist Stimulation
J. Biol. Chem.,
July 26, 2002;
277(31):
28228 - 28237.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|