Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.

Cell Communication and Signaling : CCS
Yukeyoung Kim, Sungho Ghil

Abstract

Protease-activated receptor 4 (PAR4) is a seven transmembrane G-protein coupled receptor (GPCR) activated by endogenous proteases, such as thrombin. PAR4 is involved in various pathophysiologies including cancer, inflammation, pain, and thrombosis. Although regulators of G-protein signaling (RGS) are known to modulate GPCR/Gα-mediated pathways, their specific effects on PAR4 are not fully understood at present. We previously reported that RGS proteins attenuate PAR1- and PAR2-mediated signaling through interactions with these receptors in conjunction with distinct Gα subunits. We employed a bioluminescence resonance energy transfer technique and confocal microscopy to examine potential interactions among PAR4, RGS, and Gα subunits. The inhibitory effects of RGS proteins on PAR4-mediated downstream signaling and cancer progression were additionally investigated by using several assays including ERK phosphorylation, calcium mobilization, RhoA activity, cancer cell proliferation, and related gene expression. In live cells, RGS2 interacts with PAR4 in the presence of Gαq while RGS4 binding to PAR4 occurs in the presence of Gαq and Gα12/13. Co-expression of PAR4 and Gαq induced a shift in the subcellular localization of RGS2 and RGS...Continue Reading

References

Oct 1, 1992·Trends in Biochemical Sciences·J R Hepler, A G Gilman
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·S P HeximerJ R Hepler
Apr 27, 2000·Virchows Archiv : an International Journal of Pathology·I K Bukholm, J M Nesland
May 23, 2002·The Journal of Biological Chemistry·Hiroki ChikumiJ Silvio Gutkind
May 31, 2002·Pharmacological Reviews·Morley D Hollenberg, Steven J Compton
Sep 12, 2002·Pharmacological Reviews·Susanne Hollinger, John R Hepler
Oct 10, 2002·Biochemical and Biophysical Research Communications·Chun ZhangShigetaka Kitajima
May 29, 2003·The Journal of Biological Chemistry·Stephan VogtStefan Offermanns
Jul 2, 2005·The EMBO Journal·Kiyoshi TamuraShigetaka Kitajima
Aug 13, 2005·Cellular Signalling·Anju Anne RoyPeter Chidiac
Dec 23, 2006·Cancer Research·Sowmyalakshmi SrinivasanDamodaran Chendil
Nov 17, 2007·Pharmacology & Therapeutics·Geetanjali BansalZhihui Xie
Dec 6, 2008·International Journal of Cancer. Journal International Du Cancer·Valérie GratioDalila Darmoul
Apr 29, 2010·British Journal of Pharmacology·Unice J K SohJoAnn Trejo
May 11, 2010·The Journal of Biological Chemistry·Sukru Sadik OnerJoe B Blumer
May 21, 2010·Nature·Xunwei WuG Paolo Dotto
Jun 2, 2010·International Journal of Oncology·Maria Aparecida NagaiFernando Augusto Soares
Aug 19, 2010·The Journal of Biological Chemistry·Sukru Sadik OnerStephen M Lanier
Jun 4, 2011·The International Journal of Biochemistry & Cell Biology·Yong ZhangYun Zhang
Jan 4, 2012·Nature Reviews. Drug Discovery·Rithwik RamachandranMorley D Hollenberg
Jan 11, 2012·Current Pharmaceutical Design·Colette DenisCéline Galés
Apr 21, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Christina L HirotaWallace K MacNaughton
Jun 13, 2012·The Journal of Cell Biology·Cesare OrlandiKirill A Martemyanov
Aug 21, 2012·Neoplasia : an International Journal for Oncology Research·Mahbuba RahmanIsabella T Tai
Mar 28, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chao-Jie WangXiao-Feng Sun
Nov 26, 2013·Thrombosis Research·Kazuya HosokawaIkuro Maruyama
May 27, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhi-Yong WuShun-Chang Jiao
Feb 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·James R BayrerRobert J Fletterick
May 20, 2015·European Journal of Pharmacology·Nguyen Minh DucKa Young Chung
Nov 26, 2015·The AAPS Journal·Zhihui XieKirk M Druey

❮ Previous
Next ❯

Citations

Sep 26, 2020·Molecular Pharmacology·Harrison J McNabbBenita Sjögren
Oct 24, 2020·Biochemical and Biophysical Research Communications·Hun JangSungho Ghil
Feb 19, 2021·Pharmacology & Therapeutics·Nathalie FuentesKirk M Druey
Jul 17, 2021·Biochemical and Biophysical Research Communications·Hahoon HongSungho Ghil
Jul 28, 2021·Laboratory animal research·Jayesh V Beladiya, Anita A Mehta

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
bioluminescence
transfection
BRET
reverse transcription PCR
chip
pulldown
confocal microscopy

Software Mentioned

IMAGE J
Gene Recorder
Sigmaplot
Genesystem

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.