Adjunctive Input to the Nuclear Thyroid Hormone Receptor from the Cell Surface Receptor for the Hormone

Thyroid ◽  
2013 ◽  
Vol 23 (12) ◽  
pp. 1503-1509 ◽  
Author(s):  
Paul J. Davis ◽  
Hung-Yun Lin ◽  
Heng-Yuan Tang ◽  
Faith B. Davis ◽  
Shaker A. Mousa
Keyword(s):  
Thyroid Hormone ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Cell Surface Receptor ◽  
Surface Receptor

scholarly journals Acting via a Cell Surface Receptor, Thyroid Hormone Is a Growth Factor for Glioma Cells

2006 ◽  
Vol 66 (14) ◽  
pp. 7270-7275 ◽  
Author(s):  
Faith B. Davis ◽  
Heng-Yuan Tang ◽  
Ai Shih ◽  
Travis Keating ◽  
Lawrence Lansing ◽  
...  
Keyword(s):  
Growth Factor ◽  
Thyroid Hormone ◽  
Cell Surface ◽  
Glioma Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell

scholarly journals Constitutive Activation and Inactivation of Mutations Inducing Cell Surface Loss of Receptor and Impairing of Signal Transduction of Agonist-Stimulated Eel Follicle-Stimulating Hormone Receptor

2020 ◽  
Vol 21 (19) ◽  
pp. 7075
Author(s):  
Munkhzaya Byambaragchaa ◽  
Jeong-Soo Kim ◽  
Hong-Kyu Park ◽  
Dae-Jung Kim ◽  
Sun-Mee Hong ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Follicle Stimulating Hormone ◽  
Chinese Hamster ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Surface Receptor ◽  
Stimulating Hormone

In the present study, we investigated the signal transduction of mutants of the eel follicle-stimulating hormone receptor (eelFSHR). Specifically, we examined the constitutively activating mutant D540G in the third intracellular loop, and four inactivating mutants (A193V, N195I, R546C, and A548V). To directly assess functional effects, we conducted site-directed mutagenesis to generate mutant receptors. We measured cyclic adenosine monophosphate (cAMP) accumulation via homogeneous time-resolved fluorescence assays in Chinese hamster ovary (CHO-K1) cells and investigated cell surface receptor loss using an enzyme-linked immunosorbent assay in human embryonic kidney (HEK) 293 cells. The cells expressing eelFSHR-D540G exhibited a 23-fold increase in the basal cAMP response without agonist treatment. The cells expressing A193V, N195I, and A548V mutants had completely impaired signal transduction, whereas those expressing the R546C mutant exhibited little increase in cAMP responsiveness and a small increase in signal transduction. Cell surface receptor loss in the cells expressing inactivating mutants A193V, R546C, and A548V was clearly slower than in the cell expressing the wild-type eelFSHR. However, cell surface receptor loss in the cells expressing inactivating mutant N195I decreased in a similar manner to that of the cells expressing the wild-type eelFSHR or the activating mutant D540G, despite the completely impaired cAMP response. These results provide important information regarding the structure–function relationships of G protein-coupled receptors during signal transduction.

Mini-review: Cell surface receptor for thyroid hormone and nongenomic regulation of ion fluxes in excitable cells

2010 ◽  
Vol 99 (2) ◽  
pp. 237-239 ◽  
Author(s):  
Paul J. Davis ◽  
Min Zhou ◽  
Faith B. Davis ◽  
Larry Lansing ◽  
Shaker A. Mousa ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cell Surface ◽  
Ion Fluxes ◽  
Cell Surface Receptor ◽  
Excitable Cells ◽  
Surface Receptor

scholarly journals Evidence that the thyrotropin-releasing hormone receptor and its ligand are recycled dissociated from each other

1995 ◽  
Vol 306 (1) ◽  
pp. 107-113 ◽  
Author(s):  
C P Petrou ◽  
A H Tashjian
Keyword(s):  
Cell Surface ◽  
Hormone Receptor ◽  
Thyrotropin Releasing Hormone ◽  
Cell Surface Receptor ◽  
Acidic Ph ◽  
Receptor Recycling ◽  
Bafilomycin A1 ◽  
Receptor Ligand ◽  
Surface Receptor ◽  
Receptor Pool

We have examined the trafficking of the thyrotropin-releasing hormone receptor (TRHR) and its ligand, after TRHR-TRH internalization in rat pituitary GH4C1 cells. After rapid ligand-induced receptor sequestration, the cell surface receptor pool was replenished. Replenishment was insensitive to inhibition of protein synthesis and was dependent on the duration of internalization; therefore, the replenished receptors were not newly synthesized but recycled. The total amount of recycled receptors decreased with increasing internalization time, resulting in only partial replenishment of the cell-surface receptor pool after prolonged incubation with ligand. Thus, in addition to a receptor recycling pathway, a non-cycling route exists for TRHR sorting; this route became dominant with increasing internalization periods. TRHR entry into these pathways was not determined by the affinity of the receptor-ligand interaction, because the extent of receptor recycling was similar after TRH- and methyl-TRH (MeTRH)-induced internalization. Unlike results with the TRHR, the TRH recycling pool was not depleted by the noncycling pathway. After multiple rounds of [3H]MeTRH internalization, the amount of cell-associated radioactivity increased with increasing internalization time due to accumulation of the ligand or its metabolites in a non-cycling pathway, but the absolute amount of recycled ligand remained constant after short or long internalization times. The difference in the proportion of TRHR and MeTRH that were diverted into a noncycling pathway indicated intracellular dissociation of the internalized TRHR-TRH complex. Dissociation of the internalized TRHR-TRH complex was dependent on the acidic pH in an intracellular compartment. Although extracellular acidic pH did not enhance cell-surface receptor-ligand (RL) dissociation, bafilomycin A1 inhibited both receptor and ligand recycling. We conclude that the TRHR-TRH system is unique among recycling receptors because, after RL sequestration, the TRHR-TRH complex becomes dissociated intracellularly via a bafilomycin A1-sensitive, acidic pH-dependent mechanism, and both the unoccupied TRHR and TRH recycle disassociated from each other.

scholarly journals Integrin αVβ3 Contains a Cell Surface Receptor Site for Thyroid Hormone that Is Linked to Activation of Mitogen-Activated Protein Kinase and Induction of Angiogenesis

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2864-2871 ◽  
Author(s):  
Joel J. Bergh ◽  
Hung-Yun Lin ◽  
Lawrence Lansing ◽  
Seema N. Mohamed ◽  
Faith B. Davis ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Cell Surface ◽  
Matrix Protein ◽  
Integrin Αvβ3 ◽  
Recognition Site ◽  
Cell Surface Receptor ◽  
Extracellular Matrix Protein ◽  
Surface Receptor ◽  
A Cell

Abstract Integrin αVβ3 is a heterodimeric plasma membrane protein whose several extracellular matrix protein ligands contain an RGD recognition sequence. This study identifies integrin αVβ3 as a cell surface receptor for thyroid hormone [l-T4 (T4)] and as the initiation site for T4-induced activation of intracellular signaling cascades. Integrin αVβ3 dissociably binds radiolabeled T4 with high affinity, and this binding is displaced by tetraiodothyroacetic acid, αVβ3 antibodies, and an integrin RGD recognition site peptide. CV-1 cells lack nuclear thyroid hormone receptor, but express plasma membrane αVβ3; treatment of these cells with physiological concentrations of T4 activates the MAPK pathway, an effect inhibited by tetraiodothyroacetic acid, RGD peptide, and αVβ3 antibodies. Inhibitors of T4 binding to the integrin also block the MAPK-mediated proangiogenic action of T4. T4-induced phosphorylation of MAPK is inhibited by small interfering RNA knockdown of αV and β3. These findings suggest that T4 binds to αVβ3 near the RGD recognition site and show that hormone-binding to αVβ3 has physiological consequences.

Cell-surface receptor for thyroid hormone and tumor cell proliferation

2006 ◽  
Vol 1 (6) ◽  
pp. 753-761 ◽  
Author(s):  
Paul J Davis ◽  
Faith B Davis ◽  
Hung-Yun Lin ◽  
Joel J Bergh ◽  
Shaker Mousa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Cell Surface ◽  
Tumor Cell ◽  
Cell Surface Receptor ◽  
Tumor Cell Proliferation ◽  
Surface Receptor

scholarly journals TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor

2021 ◽  
Author(s):  
Skylar J. Ferrara ◽  
Priya Chaudhary ◽  
Margaret J. DeBell ◽  
Gail Marracci ◽  
Hannah Miller ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Thyroid Hormone Receptor ◽  
Myeloid Cells ◽  
Clinical Score ◽  
Therapeutic Benefit ◽  
Cell Surface Receptor ◽  
Endocrine Regulation ◽  
Inflammatory Phenotype ◽  
Surface Receptor

AbstractTriggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype. Thyroid hormone agonism was also found to induce phagocytic behavior in microglia, a phenotype consistent with activation of the TREM2 pathway. The thyroid hormone antagonist NH-3 blocks the anti-inflammatory effects of thyroid hormone agonists and suppresses microglia phagocytosis. Finally, in a murine experimental autoimmune encephalomyelitis (EAE) multiple sclerosis model, treatment with Sob-AM2, a CNS-penetrating sobetirome prodrug, results in increased Trem2 expression in disease lesion resident myeloid cells which correlates with therapeutic benefit in the EAE clinical score and reduced damage to myelin. Our findings represent the first report of endocrine regulation of TREM2 and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents.

Expression, function, and localization of the REG cell surface receptor

2001 ◽  
Vol 120 (5) ◽  
pp. A18-A19
Author(s):  
B DIECKGRAEFE ◽  
C HOUCHEN ◽  
H ZHANG
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor
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