HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks

2006 ◽  
Vol 27 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Henry F. Vischer ◽  
Rob Leurs ◽  
Martine J. Smit
Keyword(s):  
G Protein ◽  
Cellular Signaling ◽  
G Protein Coupled Receptors ◽  
Signaling Networks ◽  
G Protein Coupled ◽  
Constitutively Active

Identification Methods of G Protein-Coupled Receptors

2011 ◽  
Vol 2 (4) ◽  
pp. 35-52
Author(s):  
Meriem Zekri ◽  
Karima Alem ◽  
Labiba Souici-Meslati
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Pharmaceutical Research ◽  
G Protein Coupled Receptors ◽  
Machine Learning Algorithms ◽  
Signaling Networks ◽  
Identification Methods ◽  
Physiological Processes ◽  
Cell Signaling Networks ◽  
G Protein Coupled

The G protein-coupled receptors (GPCRs) include one of the largest and most important families of multifunctional proteins known to molecular biology. They play a key role in cell signaling networks that regulate many physiological processes, such as vision, smell, taste, neurotransmission, secretion, immune responses, metabolism, and cell growth. These proteins are thus very important for understanding human physiology and they are involved in several diseases. Therefore, many efforts in pharmaceutical research are to understand their structures and functions, which is not an easy task, because although thousands GPCR sequences are known, many of them remain orphans. To remedy this, many methods have been developed using methods such as statistics, machine learning algorithms, and bio-inspired approaches. In this article, the authors review the approaches used to develop algorithms for classification GPCRs by trying to highlight the strengths and weaknesses of these different approaches and providing a comparison of their performances.

Constitutively Active Mutations of G Protein-Coupled Receptors

1999 ◽  
Vol 30 (6) ◽  
pp. 501-509 ◽  
Author(s):  
Verena Nordhoff ◽  
Jörg Gromoll ◽  
Manuela Simoni
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Constitutively Active

scholarly journals An Intracellular Loop (IL2) Residue Confers Different Basal Constitutive Activities to the Human Lutropin Receptor and Human Thyrotropin Receptor through Structural Communication between IL2 and Helix 6, via Helix 3

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1705-1717 ◽  
Author(s):  
Xiuyan Feng ◽  
Thomas Müller ◽  
Dario Mizrachi ◽  
Francesca Fanelli ◽  
Deborah L. Segaloff
Keyword(s):  
G Protein ◽  
Structural Model ◽  
G Protein Coupled Receptors ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Solvent Exposure ◽  
Lutropin Receptor ◽  
Reciprocal Arrangement ◽  
G Protein Coupled ◽  
Constitutively Active

The human lutropin receptor (hLHR) and human TSH receptor (hTSHR) are G protein-coupled receptors that play key roles in reproductive and thyroid physiology, respectively. We show using a quantitative assessment of cAMP production as a function of cell surface receptor expression that the hTSHR possesses greater basal constitutive activity than the hLHR. Further studies were undertaken to test the hypothesis that different potential Gs-coupling motifs identified in IL2 of the hTSHR and hLHR contribute to their different basal constitutive activities. Although mutating the receptors to interchange their potential Gs-coupling motifs reversed their relative activities, we show this to be due to the swapping of one IL2 residue (Q476 in the hLHR; R531 in the hTSHR). Molecular dynamics simulations show that the effect of the hLHR(Q476R) mutation, switching the structural features of the hLHR toward those of the hTSHR, is greater than the switching effect of the hTSHR(R531Q) mutant toward the hLHR. The structural model of the hLHR(Q476R) mutant can be considered as a hybrid of wild-type (wt) hTSHR and constitutively active mutant hLHR forms. In this hLHR(Q476R) mutant, IL2 adopts a structure similar to IL2 of the wt hTSHR, but it shares with the hLHR constitutively active mutant the solvent exposure and the reciprocal arrangement of helices 3, 5, and 6, including the weakening of the wt native R3.50-D6.30 interaction. Our results suggest a H3-mediated structural connection between IL2 and the cytosolic extension of H6. Thus, IL2 contributes significantly to the inactive and active state ensembles of these G protein-coupled receptors.

Agonist-independent regulation of constitutively active G-protein-coupled receptors

1998 ◽  
Vol 23 (11) ◽  
pp. 418-422 ◽  
Author(s):  
Rob Leurs ◽  
Martine J Smit ◽  
Astrid E Alewijnse ◽  
Henk Timmerman
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Constitutively Active

scholarly journals Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Mark von Zastrow ◽  
Alexander Sorkin
Keyword(s):  
Tyrosine Kinase ◽  
Cell Biology ◽  
Cellular Signaling ◽  
G Protein Coupled Receptors ◽  
Signaling Networks ◽  
Annual Review ◽  
Publication Date ◽  
G Protein Coupled ◽  
Multiple Receptor ◽  
Present Understanding

Intricate relationships between endocytosis and cellular signaling, first recognized nearly 40 years ago through the study of tyrosine kinase growth factor receptors, are now known to exist for multiple receptor classes and to affect myriad physiological and developmental processes. This review summarizes our present understanding of how endocytosis orchestrates cellular signaling networks, with an emphasis on mechanistic underpinnings and focusing on two receptor classes—tyrosine kinase and G protein–coupled receptors—that have been investigated in particular detail. Together, we believe that these examples provide a useful survey of the current consensus, uncertainties, and controversies in this rapidly advancing area of cell biology. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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