scholarly journals Binding of α-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway

1998 ◽  
Vol 331 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Joseph J. BUGGY
Keyword(s):  
G Protein ◽  
Protein Tyrosine Kinase ◽  
Cellular Proliferation ◽  
B Lymphocyte ◽  
Janus Kinase ◽  
Lymphocyte Function ◽  
Amino Acid Peptide ◽  
Melanocyte Stimulating Hormone ◽  
G Protein Coupled ◽  
Stimulating Hormone

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino-acid peptide with a variety of physiological effects, including the stimulation of melanocyte proliferation and melanogenesis, temperature control, control of prolactin release and the modulation of cytokine action in the immune system. There are five known subtypes of G-protein-coupled receptors, which bind with different affinities to α-MSH. This paper provides evidence that Ba/F3 pro-B-lymphocyte cells express the gene for the melanocortin 5 (MC5) receptor and specifically bind α-MSH. Western-blot analysis reveals that α-MSH binding stimulates Janus kinase 2 (JAK2) and signal transducers and activators of transcription (STAT1) tyrosine phosphorylation in both Ba/F3 cells and human cultured IM-9 lymphocytes. α-MSH is further revealed to activate JAK2 in mouse L-cells stably expressing the human MC5 receptor. Finally, α-MSH binding is shown to result in an enhancement of cellular proliferation. These findings identify a new protein tyrosine kinase pathway in the action of α-MSH, and suggest that α-MSH plays an important role in B-lymphocyte function via the activation of the same intracellular phosphorylation pathway used by cytokines and growth factors.

scholarly journals Lysophospholipid Growth Factors and Their G Protein-Coupled Receptors in Immunity, Coronary Artery Disease, and Cancer

2002 ◽  
Vol 2 ◽  
pp. 324-338 ◽  
Author(s):  
Edward J. Goetzl ◽  
Markus Graeler ◽  
Mei-Chuan Huang ◽  
Geetha Shankar
Keyword(s):  
Growth Factors ◽  
Tumor Cells ◽  
G Protein ◽  
Neural Development ◽  
Cellular Proliferation ◽  
Biological Fluids ◽  
Functional Responses ◽  
Cancer Data ◽  
S1p Receptors ◽  
G Protein Coupled

The physiological lysophospholipids (LPLs), exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are omnific mediators of normal cellular proliferation, survival, and functions. Although both LPA and S1P attain micromolar concentrations in many biological fluids, numerous aspects of their biosynthesis, transport, and metabolic degradation are unknown. Eight members of a new subfamily of G protein-coupled LPA/S1P receptors, originally termed Edg Rs, bind either LPA or S1P with high affinity and transduce a series of growth-related and/or cytoskeleton-based functional responses. The most critical areas of LPL biology and pathobiology are neural development and neurodegeneration, immunity, atherosclerosis and myocardial injury, and cancer. Data from analyses of T cells established two basic points: (1) the plasticity and adaptability of expression of LPA/S1P Rs by some cells as a function of activation, and (2) the role of opposing signals from two different receptors for the same ligand as a mechanism for fine control of effects of LPLs. In the heart, LPLs may promote coronary atherosclerosis, but are effectively cytoprotective for hypoxic cardiac myocytes and those exposed to oxygen free radicals. The findings of production of LPA by some types of tumor cells, overexpression of selected sets of LPA receptors by the same tumor cells, and augmentation of the effects of protein growth factors by LPA have suggested pathogenetic roles for the LPLs in cancer. The breadth of physiologic and pathologic activities of LPLs emphasizes the importance of developing bioavailable nonlipid agonists and antagonists of the LPA/S1P receptors for diverse therapeutic applications.

scholarly journals Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2

2006 ◽  
Vol 26 (20) ◽  
pp. 7550-7560 ◽  
Author(s):  
Alison R. Meloni ◽  
Gregory B. Fralish ◽  
Patrick Kelly ◽  
Ali Salahpour ◽  
James K. Chen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Sonic Hedgehog ◽  
Cellular Proliferation ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Positive Role ◽  
Proliferation And Differentiation ◽  
Hedgehog Proteins ◽  
G Protein Coupled

ABSTRACT Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli. The activity of mammalian Smoothened is controlled by three different hedgehog proteins, Indian, Desert, and Sonic hedgehog, through their interaction with the Smoothened inhibitor Patched. However, the mechanisms of signal transduction from Smoothened are poorly understood. We show that a kinase which regulates signaling by many “conventional” 7TM G-protein-coupled receptors, G protein-coupled receptor kinase 2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2. We find that GRK2 promotes the association between active Smoothened and β-arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of Smoothened and GRK2, is diminished by β-arrestin 2 knockdown with shRNA. Together, these data suggest that GRK2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between β-arrestin 2 and Smoothened.

Kinase-Inactive G-Protein-Coupled Receptor Kinases Are Able to Attenuate Follicle-Stimulating Hormone-Induced Signaling

2001 ◽  
Vol 282 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Eric Reiter ◽  
Sébastien Marion ◽  
Fabienne Robert ◽  
Carine Troispoux ◽  
François Boulay ◽  
...  
Keyword(s):  
G Protein ◽  
Follicle Stimulating Hormone ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
G Protein Coupled ◽  
Stimulating Hormone

scholarly journals Extrathyroidal Manifestations of Persistent Sporadic Non-Autoimmune Hyperthyroidism in a 6-Year-Old Boy: A Case Report

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 713
Author(s):  
Moon Bae Ahn
Keyword(s):  
G Protein ◽  
Hormone Receptor ◽  
Cell Metabolism ◽  
Receptor Gene ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cell ◽  
Gene Encoding ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
Stimulating Hormone

Thyroid-stimulating hormone receptor (TSHR) belongs in a subfamily of the G protein-coupled receptors. Thyroid-stimulating hormone receptor gene (TSHR), a gene encoding TSHR, is a major controller of thyroid cell metabolism, and its gain of function mutation leads to non-autoimmune hyperthyroidism (NAH), a condition of a prolonged state of hyperthyroidism. Diverse human diseases, and genetic, constitutional, or environmental factors contribute to the phenotypic variations of TSHR mutations; however, the underlying mechanisms leading to various extrathyroidal manifestations across ages are poorly understood. In 2018, the first Korean case of persistent sporadic NAH due to missense mutation of TSHR was reported, and this report highlights the extrathyroidal manifestations of NAH. Further investigation is warranted to clarify the roles of functional mutations of TSHR by investigating the correlation between G protein-dependent signaling properties and clinical phenotypes associated with persistent hyperthyroidism in order to develop novel therapies that could be provided for numerous conditions caused by NAH.

scholarly journals G Protein-Coupled Purinergic P2Y Receptor Oligomerization: Pharmacological Changes and Dynamic Regulation

2020 ◽  
Author(s):  
Xiaoqing Guo ◽  
Qin Li ◽  
Shulan Pi ◽  
Bo Hu ◽  
Yuanpeng Xia ◽  
...  
Keyword(s):  
G Protein ◽  
Cellular Proliferation ◽  
P2y Receptors ◽  
The Body ◽  
Pharmacological Activities ◽  
Neuroprotective Effects ◽  
Dynamic Regulation ◽  
G Protein Coupled

P2Y receptors (P2YRs), a δ group of rhodopsin-like G protein-coupled receptors (GPCRs), have many essential functions in physiology and pathology, such as platelet aggregation, immune responses, neuroprotective effects, inflammation, and cellular proliferation; thus, they are among the most researched therapeutic targets for use in the clinical treatment of diseases (e.g., clopidogrel, an antithrombotic drug, and Prolacria, a treatment for dry eye). Over the past two decades, GPCRs have been revealed to transmit signals as dimers to increase the diversity of signalling pathways or pharmacological activities. Many studies have frequently confirmed dimerization between P2YRs and other GPCRs due to their functions in cardiovascular and cerebrovascular processes in vivo and in vitro. Recently, some P2YR dimers that dynamically balance physiological functions in the body were shown to be involved in effective signal transduction and exert pathological pharmacological effects. In this review, we summarize the types, pharmacological changes, and active regulators of P2YR-related dimerization. In summary, our review delineates that P2YR-related dimers have new functions and pharmacological activities and maybe a novel direction to improve the effectiveness of medications such as thrombotic events associated with COVID-19.

scholarly journals Regulation of ERRα Gene Expression by Estrogen Receptor Agonists and Antagonists in SKBR3 Breast Cancer Cells: Differential Molecular Mechanisms Mediated by G Protein-Coupled Receptor GPR30/GPER-1

2010 ◽  
Vol 24 (5) ◽  
pp. 969-980 ◽  
Author(s):  
Yin Li ◽  
Lutz Birnbaumer ◽  
Christina T. Teng
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
G Protein ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
G Protein Coupled Receptor ◽  
Ici 182,780 ◽  
G Protein Coupled

Abstract In selected tissues and cell lines, 17β-estradiol (E2) regulates the expression of estrogen-related receptor α (ERRα), a member of the orphan nuclear receptor family. This effect is thought to be mediated by the estrogen receptor α (ERα). However in the ERα- and ERβ-negative SKBR3 breast cancer cell line, physiological levels of E2 also stimulate ERRα expression. Here, we explored the molecular mechanism that mediates estrogen action in ER-negative breast cancer cells. We observed that E2, the ERα agonist, as well as the ERα antagonists ICI 182,780 and tamoxifen (TAM), a selective ER modulator, stimulate the transcriptional activity of the ERRα gene and increase the production of ERRα protein in SKBR3 cells. Moreover, the ERRα downstream target genes expression and cellular proliferation are also increased. We show further that the G protein-coupled receptor GPR30/GPER-1 (GPER-1) mediates these effects. The GPER-1 specific ligand G-1 mimics the actions of E2, ICI 182,780, and TAM on ERRα expression, and changing the levels of GPER-1 mRNA by overexpression or small interfering RNA knockdown affected the expression of ERRα accordingly. Utilizing inhibitors, we delineate a different downstream pathway for ER agonist and ER antagonist-triggered signaling through GPER-1. We also find differential histone acetylation and transcription factor recruitment at distinct nucleosomes of the ERRα promoter, depending on whether the cells are activated with E2 or with ER antagonists. These findings provide insight into the molecular mechanisms of GPER-1/ERRα-mediated signaling and may be relevant to what happens in breast cancer cells escaping inhibitory control by TAM.

scholarly journals G protein-coupled receptor-induced Akt activity in cellular proliferation and apoptosis

FEBS Journal ◽  
2007 ◽  
Vol 274 (23) ◽  
pp. 6025-6036 ◽  
Author(s):  
David C. New ◽  
Kelvin Wu ◽  
Alice W. S. Kwok ◽  
Yung H. Wong
Keyword(s):  
G Protein ◽  
Cellular Proliferation ◽  
G Protein Coupled Receptor ◽  
Proliferation And Apoptosis ◽  
G Protein Coupled
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