scholarly journals Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer

2014 ◽  
Vol 110 (8) ◽  
pp. 2011-2020 ◽  
Author(s):  
H Q Xi ◽  
A Z Cai ◽  
X S Wu ◽  
J X Cui ◽  
W S Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
G Protein ◽  
Therapeutic Target ◽  
Human Gastric Cancer ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Potential Therapeutic Target ◽  
G Protein Coupled

scholarly journals Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase

2017 ◽  
Vol 313 (1) ◽  
pp. H149-H163 ◽  
Author(s):  
Daniela Dal-Secco ◽  
Silvia DalBó ◽  
Natalia E. S. Lautherbach ◽  
Fábio N. Gava ◽  
Mara R. N. Celes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
G Protein ◽  
Cardiac Dysfunction ◽  
Therapeutic Target ◽  
Adrenergic Receptor ◽  
Receptor Density ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Potential Therapeutic Target ◽  
G Protein Coupled

G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction. NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore, G protein-coupled receptor kinase isoform 2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.

Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in gastric cancer

2012 ◽  
Vol 63 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Kazuhiro Yamanoi ◽  
Mariko Fukuma ◽  
Hiroshi Uchida ◽  
Ryoji Kushima ◽  
Ken Yamazaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
G Protein ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Characterization of Two Fly LGR (Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor) Proteins Homologous to Vertebrate Glycoprotein Hormone Receptors: Constitutive Activation of Wild-Type Fly LGR1 But Not LGR2 in Transfected Mammalian Cells**This study was supported by NIH Grant HD-23273. The GenBank submission number for fly LGR2 is AF274591.

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Shinya Nishi ◽  
Sheau Yu Hsu ◽  
Karen Zell ◽  
Aaron J. W. Hsueh
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Coupling Mechanism ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors ◽  
Signaling Mechanisms ◽  
G Protein Coupled

Abstract The receptors for lutropin (LH), FSH, and TSH belong to the large G protein-coupled receptor (GPCR) superfamily and are unique in having a large N-terminal extracellular (ecto-) domain important for interactions with the large glycoprotein hormone ligands. Recent studies indicated the evolution of a large family of the leucine-rich repeat-containing, G protein-coupled receptors (LGRs) with at least seven members in mammals. Based on the sequences of mammalian glycoprotein hormone receptors, we have identified a new LGR in Drosophila melanogaster and named it as fly LGR2 to distinguish it from the previously reported fly LH/FSH/TSH receptor (renamed as fly LGR1). Genomic analysis indicated the presence of 10 exons in fly LGR2 as compared with 16 exons in fly LGR1. The deduced fly LGR2 complementary DNA (cDNA) showed 43 and 64% similarity to the fly LGR1 in the ectodomain and transmembrane region, respectively. Comparison of 12 LGRs from diverse species indicated that these proteins can be divided into three subfamilies and fly LGR1 and LGR2 belong to different subfamilies. Potential signaling mechanisms were tested in human 293T cells overexpressing the fly receptors. Of interest, fly LGR1, but not LGR2, showed constitutive activity as reflected by elevated basal cAMP production in transfected cells. The basal activity of fly LGR1 was further augmented following point mutations of key residues in the intracellular loop 3 or transmembrane VI, similar to those found in patients with familial male precocious puberty. The present study reports the cloning of fly LGR2 and indicates that the G protein-coupling mechanism is conserved in fly LGR1 as compared with the mammalian glycoprotein hormone receptors. The characterization of fly receptors with features similar to mammalian glycoprotein hormone receptors allows a better understanding of the evolution of this unique group of GPCRs and future elucidation of their ligand signaling mechanisms.

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