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Subtype specific β‐adrenerigic receptor‐mediated transactivation of epidermal growth factor receptor decreases apoptosis through differential activation of ERK1/2 and Akt
Author(s) -
Grisanti Laurel A,
Carter Rhonda L,
Yu Justine E,
Tilley Douglas G
Publication year - 2013
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.27.1_supplement.652.10
Subject(s) - transactivation , protein kinase b , epidermal growth factor receptor , phosphorylation , agonist , apoptosis , microbiology and biotechnology , cancer research , egfr inhibitors , chemistry , receptor , signal transduction , biology , transcription factor , biochemistry , gene
β‐adrenergic receptors (βAR) are critical regulators of cardiac function whose dysregulation during heart failure are associated with diminished cardiac function, however βAR‐mediated EGFR transactivation has been shown to relay cardioprotection via unknown mechanisms. While both β1AR and β2AR are capable of inducing EGFR transactivation the relative impact of each on cardiac function is unknown. We hypothesized that transactivation of EGFR will produce distinct cardiomyocyte signaling responses leading to decreases in apoptosis that are βAR subtype‐specific. To test this hypothesis, rat neonatal cardiomyocytes (RNCM) were treated with dobutamine (β1AR agonist) or salbutamol (β2AR agonist) in the presence or absence of the EGFR antagonist AG1478. Following 10 min stimulation, differences in ERK1/2 and Akt phosphorylation and localization were observed. Apoptosis was decreased which was abrogated with EGFR inhibition. EGFR‐transactivation by βAR decreased apoptosis through ERK1/2 and Akt pathways. These results demonstrate differential impact of β1AR and β2AR‐mediated EGFR transactivation on the subcellular activation of ERK1/2 and Akt and the regulation of cell death in cardiomyocytes.