Evidence of an important and direct role for protein kinase C in agonist-induced phosphorylation leading to desensitization of the angiotensin AT1A receptor

British Journal of Pharmacology
A J BalmforthS G Ball

Abstract

1. The role of protein kinase C (PKC) in the mechanism underlying rapid agonist-induced desensitization of angiotensin AT1 receptors remains unresolved. A major problem has been to isolate these receptors in a sufficiently purified form to allow study of their phosphorylation state. 2. A cleavable (His)6 affinity tag was introduced into the N-terminus of the recombinant AT1A receptor and stably expressed in human embryonic kidney cells. This affinity tag allowed rapid isolation, purification and determination of the phosphorylation state of the AT1A receptor. Using these cells, we determined the role of PKC in both agonist-induced receptor phosphorylation and desensitization under identical conditions. 3. Agonist-induced phosphorylation of the AT1A receptor was observed at both low and high concentrations of angiotensin II (AII). Preincubation of cells with Ro-31-8220 (a PKC specific inhibitor) revealed that at low concentrations of AII (1 nM), PKC appeared to be the main kinase involved in receptor phosphorylation. In contrast, at high concentrations of AII (100 nM), although PKC-mediated phosphorylation of the receptor was observed, this was overshadowed by a second kinase. 4. In preliminary desensitization studies we observe...Continue Reading

References

Nov 2, 1992·European Journal of Pharmacology·H P WintersgillA J Balmforth
May 29, 1992·Biochemical and Biophysical Research Communications·H SasamuraV J Dzau
Oct 1, 1991·Trends in Biochemical Sciences·K Palczewski, J L Benovic
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R JanknechtH G Stunnenberg
Feb 1, 1991·Trends in Pharmacological Sciences·P B TimmermansW F Herblin
May 1, 1989·Molecular and Cellular Endocrinology·M Tencé, A Petit
Feb 1, 1987·Molecular Endocrinology·M C CarsonK J Catt
Jan 1, 1995·Vitamins and Hormones·R Sterne-Marr, J L Benovic
Dec 1, 1994·Kidney International·H SasamuraR E Pratt
Oct 15, 1995·European Journal of Pharmacology·A J BalmforthS G Ball

❮ Previous
Next ❯

Citations

Mar 15, 2005·Biochemical Pharmacology·Nambi AiyarStephen A Douglas
Sep 1, 2000·Regulatory Peptides·L HunyadyZ Gáborik
Feb 4, 1999·Regulatory Peptides·W G Thomas
Oct 20, 2001·Cell Research·D F GuoT Inagami
Oct 2, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Flávia Fernandes MesquitaPatrícia Aline Boer
Apr 1, 1999·Annual Review of Physiology·M BünemannM M Hosey
Jul 3, 2002·The Journal of Clinical Investigation·Zhonghua QiMatthew D Breyer
Apr 25, 2012·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Juan GaoLie Gao
Dec 20, 2013·International Journal of Molecular Sciences·Anastasios Lymperopoulos, Shmuel Negussie
Mar 27, 2004·Physiological Reviews·András Spät, László Hunyady
Jun 2, 2011·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Silmara CiamponeJosé A R Gontijo
Mar 12, 2011·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Adriana ZapparoliJosé Antonio Rocha Gontijo
Oct 19, 2001·Endocrinology·A Hus-CitharelC Llorens-Cortes
Apr 12, 2003·Journal of Receptor and Signal Transduction Research·Andrea Hoffmann, David R Cool
Jan 5, 2017·Journal of Developmental Origins of Health and Disease·V H G RizziP A Boer
Nov 18, 2000·American Journal of Physiology. Cell Physiology·J G MeszarosL L Brunton
Apr 25, 2000·The Journal of Biological Chemistry·S J Mundell, J L Benovic
Nov 24, 1999·The American Journal of Physiology·G B WillarsS R Nahorski
Aug 14, 2002·British Journal of Anaesthesia·M J Rebecchi, S N Pentyala
Apr 16, 2008·European Journal of Pharmacology·Mariëlle C Hendriks-BalkAstrid E Alewijnse

❮ Previous
Next ❯

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.