Effect of acute acid-base disturbances on the phosphorylation of phospholipase C-γ1 and Erk1/2 in the renal proximal tubule

Physiological Reports
Lara A Skelton, Walter F Boron

Abstract

The renal proximal tubule (PT) plays a major role in whole-body pH homeostasis by secreting H(+) into the tubule lumen. Previous work demonstrated that PTs respond to basolateral changes in [CO2] and [HCO3-] by appropriately altering H(+) secretion-responses blocked by the ErbB inhibitor PD168393, or by eliminating signaling through AT1 angiotensin receptors. In the present study, we analyze phosphorylation of three downstream targets of both ErbBs and AT1: phospholipase C-γ1 (PLC-γ1), extracellular-regulated kinase 1 (Erk1), and Erk2. We expose rabbit PT suspensions for 5 and 20 min to our control (Ctrl) condition (5% CO2, 22 mmol/L HCO3-, pH 7.40) or one of several conditions that mimic acid-base disturbances. We found that each disturbance produces characteristic phosphorylation patterns in the three enzymes. For example, respiratory acidosis (elevated [CO2], normal [HCO3-]) at 20 min decreases PLC-γ1 phosphorylation at tyrosine-783 (relative to Ctrl). Metabolic acidosis (normal [CO2], decreased [HCO3-]) for 5 min increases Erk1 phosphorylation (p-Erk1) but not p-Erk2, whereas metabolic alkalosis (normal [CO2], elevated [HCO3-]) for 5 min decreases p-Erk1 and p-Erk2. In the presence of CO2/HCO3-, PD168393 blocks only two of ...Continue Reading

References

Jan 1, 1983·The Journal of General Physiology·W F Boron, E L Boulpaep
Jan 1, 1996·Annual Review of Physiology·S L GluckB S Lee
Sep 23, 1997·Cell·B J CanagarajahE J Goldsmith
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·J SchnermannA S Verkman
Dec 9, 1998·Kidney International·J P LeaJ M Sands
Oct 4, 2000·Physiological Reviews·M J Rebecchi, S N Pentyala
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Nov 13, 2001·American Journal of Physiology. Renal Physiology·T WangG Giebisch
Jun 26, 2002·Kidney International·Hirohiko TsuganezawaRobert J Alpern
Nov 28, 2002·Nature Genetics·John Quackenbush
Oct 1, 1953·The Journal of Clinical Investigation·A S RELMANW B SCHWARTZ
Oct 1, 1953·The American Journal of Physiology·P BRAZEAU, A GILMAN
Jan 1, 1954·The Journal of Clinical Investigation·P J DORMANR F PITTS
Sep 25, 2003·Physiological Reviews·Mitchell Chesler
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yuehan ZhouWalter F Boron
Mar 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Benoit PoulinSue Goo Rhee
Oct 6, 2005·American Journal of Physiology. Renal Physiology·Yuehan ZhouWalter F Boron
Oct 22, 2005·The Biochemical Journal·Matilda Katan
Dec 27, 2005·Gene·Nicola NormannoDavid S Salomon
May 18, 2006·American Journal of Physiology. Renal Physiology·Yuehan ZhouWalter F Boron
Aug 18, 2006·Journal of the American Society of Nephrology : JASN·Walter F Boron
Jan 24, 2007·The Biochemical Journal·Tony Tiganis, Anton M Bennett
Mar 16, 2007·American Journal of Physiology. Renal Physiology·Yuehan ZhouWalter F Boron
Oct 5, 2007·American Journal of Physiology. Renal Physiology·Yuehan Zhou, Walter F Boron
Dec 21, 2007·Journal of the American Society of Nephrology : JASN·Yuehong LiToshiro Fujita
Aug 5, 2010·Pflügers Archiv : European journal of physiology·Martin TresguerresLonny R Levin
Mar 1, 2012·Journal of the American Society of Nephrology : JASN·Dennis Brown, Carsten A Wagner
May 25, 2013·American Journal of Physiology. Cell Physiology·Nicholas C ZachosMark Donowitz
Oct 18, 2013·American Journal of Physiology. Renal Physiology·Lara A Skelton, Walter F Boron
Nov 26, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski

❮ Previous
Next ❯

Citations

Apr 26, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Stine F PedersenLuis A Pardo
Mar 27, 2018·Acta Physiologica·M FlinckS F Pedersen
Nov 26, 2015·Clinical Journal of the American Society of Nephrology : CJASN·L Lee HammKathleen S Hering-Smith
Sep 20, 2019·Intensive Care Medicine Experimental·Aritz Perez Ruiz de GaribayBernhard Kreymann
Jul 25, 2019·Cells·Kimberly F AtkinsonSurya M Nauli

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
protein assay
electrophoresis
X-ray

Software Mentioned

Excel
ImageJ

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.