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Epidermal Growth Factor Receptor activates ERK but not JNK through a Ras independent pathway during cardiomyocyte stretch
Author(s) -
Duquesnes Nicolas,
Morel Eric,
Lezoualc’h Frank,
Crozatier Bertrand
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.50
Subject(s) - mapk/erk pathway , kinase , microbiology and biotechnology , phosphorylation , protein kinase b , epidermal growth factor , mitogen activated protein kinase , chemistry , receptor tyrosine kinase , cancer research , signal transduction , tyrosine kinase , medicine , endocrinology , biology , receptor , biochemistry
We evaluated the Mitogen Activated Protein kinases (MAPK) pathways activated during stretch, a major determinant of ventricular hypertrophy, in neonatal rat ventricular cardiac myocytes in culture. The activations of Ras, ERK and JNK peaked 15 min after the initiation of stretch, suggesting a cause‐effect relationship. A dominant negative form of Ras did not inhibit stretch‐induced ERK and JNK activations showing that Ras was not involved in MAPK stimulation. Among the pathways that activate MAPK, tyrosine kinases were shown to play a major role. Genistein, a tyrosine kinase inhibitor, significantly decreased both ERK and JNK activations during stretch but did not inhibit Ras. The epidermal growth factor receptor (EGFR) is one of the tyrosine kinase receptors. We examined its role using a specific blocker, AG1478. It decreased both basal ERK phosphorylation through the Ras‐Raf1‐MEK cascade and stretch‐induced ERK activation independently of this cascade. In contrast with its effects on ERK, AG1478 did not significantly modify JNK phosphorylation both in basal conditions and during stretch. In addition, our data show that the PI3 kinase‐Akt /PKB pathway is downstream of the EGFR, participating in ERK but not JNK activation. We conclude that the EGFR acts on ERK phosphorylation through 2 different pathways: in basal conditions through the Ras pathway and during stretch through the PI3kinase pathway.