Ras Regulates NFAT3 Activity in Cardiac Myocytes
Key result
Expression of a constitutively active form of Ras in neonatal cardiac myocytes increased NFAT activity and nuclear translocation, demonstrating a functional interaction between Ras and calcineurin pathways.
Population
Neonatal cardiac myocytes
Comparison
Expression of constitutively active Ras… vs Expression of activating mutants of Rac1, RhoA…
Design
Preclinical
Authors
Discussion
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Implication
Preclinical only; leaves open whether Ras-calcineurin crosstalk drives human cardiac hypertrophy.
Structured PICO
P
Population
Neonatal cardiac myocytes
I
Intervention
Expression of constitutively active Ras (V12ras), dominant negative ras, or pharmacological/genetic manipulation of MEK1, c-Raf, ERK2, and calcineurin
C
Comparator
Expression of activating mutants of Rac1, RhoA, or Cdc42, or untreated controls
O
Outcome
NFAT transcriptional activity and NFAT3 nuclear localizationsurrogate
In cardiac myocytes, a Ras-regulated pathway involving MAPK stimulation regulates NFAT3 activity upstream of calcineurin, linking two distinct hypertrophic pathways.
Cite This Study
Ichida et al. (2001) studied Cardiac myocyte hypertrophy. Constitutively active form of Ras (V12ras) vs. Activating mutants of Rac1, RhoA, or Cdc42; dominant negative ras was evaluated on NFAT activity and nuclear translocation. Expression of a constitutively active form of Ras in neonatal cardiac myocytes increased NFAT activity and nuclear translocation, demonstrating a functional interaction between Ras and calcineurin pathways.