Ras triggers acidosis-induced activation of the extracellular-signal- regulated kinase pathway in cardiac myocytes
Biochemical Journal, ISSN: 0264-6021, Vol: 399, Issue: 3, Page: 493-501
2006
- 28Citations
- 18Captures
Metric Options: Counts1 Year3 YearSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations28
- Citation Indexes28
- 28
- CrossRef27
- Captures18
- Readers18
- 18
Article Description
In cardiac myocytes, sustained (3 min) intracellular acidosis activates the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway and, through this pathway, increases sarcolemmal NHE (NaTH exchanger) activity [Haworth, McCann, Snabaitis, Roberts and Avkiran (2003) J. Biol. Chem. 278, 31676-31684]. In the present study, we aimed to determine the time-dependence, pH-dependence and upstream signalling mechanisms of acidosis-induced ERK1/2 activation in ARVM (adult rat ventricular myocytes). Cultured ARVM were subjected to intracellular acidosis for up to 20 min by exposure to NHCl, followed by washout with a bicarbonate-free Tyrode solution containing the NHE1 inhibitor cariporide. After the desired duration of intracellular acidosis, the phosphorylation status of ERK1/2 and its downstream effector p90 (90 kDa ribosomal S6 kinase) were determined by Western blotting. This revealed a time-dependent transient phosphorylation of both ERK1/2 and p90 by intracellular acidosis (intracellular pH ∞6.6), with maximum activation occurring at 3 min and a return to basal levels by 20 min. When the degree of intracellular acidosis was varied from ∼6.8 to ∼6.5, maximum ERK1/2 phosphorylation was observed at an intracellular pH of 6.64. Inhibition of MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK kinase 1/2) by pre-treatment of ARVM with U0126 or adenoviral expression of dominant-negative D208A-MEK1 protein prevented the phosphorylation of ERK1/2 by sustained intracellular acidosis, as did inhibition of Raf-1 with GW 5074 or ZM 336372. Interference with Ras signalling by the adenoviral expression of dominant-negative N17-Ras protein or with FPT III (farnesyl protein transferase inhibitor III) also prevented acidosis-induced ERK1/2 phosphorylation, whereas inhibiting G-protein signalling [by adenoviral expression of RGS4 or Lsc, the RGS domain of p115 RhoGEF (guanine nucleotide-exchange factor)] or protein kinase C (with bisindolylmaleimide I) had no effect. Our data show that, in ARVM, sustained intracellular acidosis activates ERK1/2 through proximal activation of the classical Ras/Raf/MEK pathway. © 2006 Biochemical Society.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33750566657&origin=inward; http://dx.doi.org/10.1042/bj20051628; http://www.ncbi.nlm.nih.gov/pubmed/16831126; http://biochemj.org/lookup/doi/10.1042/BJ20051628; https://portlandpress.com/biochemj/article/399/3/493/41827/Ras-triggers-acidosis-induced-activation-of-the; https://dx.doi.org/10.1042/bj20051628; https://portlandpress.com/biochemj/article-abstract/399/3/493/41827/Ras-triggers-acidosis-induced-activation-of-the?redirectedFrom=fulltext; https://portlandpress.com/biochemj/article/399/3/493/41827/Ras-triggers-acidosisinduced-activation-of-the; https://portlandpress.com/biochemj/article-pdf/399/3/493/646035/bj3990493.pdf; http://www.biochemj.org/content/399/3/493; http://www.biochemj.org/content/399/3/493.abstract; http://www.biochemj.org/content/399/3/493.full.pdf; http://www.biochemj.org/cgi/doi/10.1042/BJ20051628; http://www.biochemj.org/bj/399/bj3990493.htm
Portland Press Ltd.
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know