![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 56, Issue 2, 316-324, August 1999
1B-Adrenergic, and
A1 Adenosine Receptor-Mediated Responses
Consorzio Mario Negri Sud, Istituto di Ricerche Farmacologiche
"Mario Negri," Santa Maria Imbaro, Italy
G protein-coupled receptor kinases (GRKs) play a key role in the
process of receptor homologous desensitization. In the present study,
we address the question of whether a variety of receptors coupled to
different G protein subtypes and naturally expressed on the same cell
are selectively regulated by GRK2. The signaling stimulated by
thyrotropin (TSH), 
1B-adrenergic, and A1
adenosine receptors was studied in FRTL-5 cells permanently transfected to overexpress GRK2 and GRK2-K220R, a kinase dead GRK dominant negative
mutant. In FRTL-5 overexpressing GRK2, TSH-induced cyclic AMP response
was attenuated, indicating that TSH receptor is desensitized by this
kinase. Consistently, FRTL-5 cells overexpressing GRK2-K220R show
increased TSH-induced cyclic AMP response, demonstrating that this
receptor is under tonic control by GRK. Unlike TSH receptor, 1B-adrenergic receptor response was unaffected in FRTL-5
overexpressing GRK2 and GRK2-K220R. When A1 adenosine
receptors were stimulated, Gi
-mediated cyclic AMP
inhibition was totally unaffected by overexpression of either GRK2 or
GRK2-K220R. By contrast, G
-mediated response
(activation of mitogen-activated protein kinases) was efficiently
desensitized by GRK2 but was unaffected by GRK2-K220R overexpression.
The present study documents that overexpression of GRK2 results in a
selective regulation of different G protein-coupled receptors expressed
on the same cell and that this kinase can regulate preferentially only
one of the different pathways activated by the same receptor. The
preferential regulation of the A1 adenosine receptor-stimulated mitogen-activated protein kinases by GRK2 indicates
that this kinase can have additional regulatory effects on
G-stimulated pathways, possibly through direct
binding and regulation of the receptor-G complex.
This article has been cited by other articles:
|
|
 |
|
  T. Metaye, P. Levillain, J.-L. Kraimps, and R. Perdrisot Immunohistochemical detection, regulation and antiproliferative function of G-protein-coupled receptor kinase 2 in thyroid carcinomas J. Endocrinol., July 1, 2008; 198(1): 101 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhou, M. F. A. Livak, M. Bernier, D. C. Muller, O. D. Carlson, D. Elahi, S. Maudsley, and J. M. Egan Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E538 - E547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Molina-Munoz, M. T. Romero-Avila, and J. A. Garcia-Sainz Insulin-Like Growth Factor-I Induces {alpha}1B-Adrenergic Receptor Phosphorylation through G{beta}{gamma} and Epidermal Growth Factor Receptor Transactivation Mol. Endocrinol., November 1, 2006; 20(11): 2773 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gros, Q. Ding, J. Chorazyczewski, J. Andrews, J. G. Pickering, R. A. Hegele, and R. D. Feldman The Impact of Blunted beta-Adrenergic Responsiveness on Growth Regulatory Pathways in Hypertension Mol. Pharmacol., January 1, 2006; 69(1): 317 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Iacovelli, L. Capobianco, M. Iula, V. Di Giorgi Gerevini, A. Picascia, J. Blahos, D. Melchiorri, F. Nicoletti, and A. De Blasi Regulation of mGlu4 Metabotropic Glutamate Receptor Signaling by Type-2 G-Protein Coupled Receptor Kinase (GRK2) Mol. Pharmacol., May 1, 2004; 65(5): 1103 - 1110. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Metaye, E. Menet, J. Guilhot, and J.-L. Kraimps Expression and Activity of G Protein-Coupled Receptor Kinases in Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3279 - 3286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Eckhart and W. J. Koch Transgenic Studies of Cardiac Adrenergic Receptor Regulation J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 1 - 5. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Dautzenberg, S. Braun, and R. L. Hauger GRK3 mediates desensitization of CRF1 receptors: a potential mechanism regulating stress adaptation Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R935 - R946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. SALLESE, L. SALVATORE, E. D’URBANO, G. SALA, M. STORTO, T. LAUNEY, F. NICOLETTI, T. KNÖPFEL, and A. DE BLASI The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1 FASEB J, December 1, 2000; 14(15): 2569 - 2580. [Abstract] [Full Text]
|
|
|
|
|
|
M. Sallese, S. Mariggiò, E. D'Urbano, L. Iacovelli, and A. De Blasi Selective Regulation of Gq Signaling by G Protein-Coupled Receptor Kinase 2: Direct Interaction of Kinase N Terminus with Activated Galpha q Mol. Pharmacol., April 1, 2000; 57(4): 826 - 831. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. D. Eckhart, S. J. Duncan, R. B. Penn, J. L. Benovic, R. J. Lefkowitz, and W. J. Koch Hybrid Transgenic Mice Reveal In Vivo Specificity of G Protein-Coupled Receptor Kinases in the Heart Circ. Res., January 7, 2000; 86(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Horie and P. A. Insel Retrovirally Mediated Transfer of a G Protein-coupled Receptor Kinase (GRK) Dominant-negative Mutant Enhances Endogenous Calcitonin Receptor Signaling in Chinese Hamster Ovary Cells. GRK INHIBITION ENHANCES EXPRESSION OF RECEPTORS AND RECEPTOR mRNA J. Biol. Chem., September 15, 2000; 275(38): 29433 - 29440. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
