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ERK activation by mechanical strain is regulated by the small G proteins rac‐1 and rhoA
Author(s) -
Laboureau Julien,
Dubertret Louis,
LebretonDe Coster Corinne,
Coulomb Bernard
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00117.x
Subject(s) - rhoa , mapk/erk pathway , transfection , effector , microbiology and biotechnology , strain (injury) , chemistry , enzyme activator , kinase , signal transduction , biochemistry , biology , anatomy , gene
Physical forces play an important role in regulating cell functions. We applied mechanical strain to human fibroblasts by magnetic attraction of superparamagnetic arginine‐glycine‐aspartic acid (RGD)‐coated beads. We confirmed that the MAP kinases Erk and p38 are activated by mechanical strain, and went further by demonstrating the activation of Elk‐1 by mechanical strain, mainly through a MEK‐Erk pathway. Transfection of a dominant negative form of the G protein rac‐1 (rac T17N), and inhibition of PI3K, an effector of rac‐1, efficiently prevented Elk‐1 activation by mechanical forces. Transfection with C3 transferase, known to inhibit rhoA, and inhibition of rock (a downstream effector of rhoA), gave similar results. However, contrary to the active form of rhoA (rho G14V), transfection of the active form of rac‐1 (rac G12V) induced Elk activation and mimicked the effects of mechanical strain. These results point out that the two small G proteins rhoA and rac‐1 participate in cell sensitivity to mechanical strain and lead to the modulation of the Erk pathway.