Stimulation of the four isoforms of receptor tyrosine kinase ErbB4, but not ErbB1, confers cardiomyocyte hypertrophy
Zhen Wang, Hsiu-Wen Chan, Giovanna Gambarotta, Nicola J Smith, Brooke W Purdue, David J Pennisi, Enzo R Porrello, Shannon L O'Brien, Melissa E Reichelt, Walter G Thomas, Tamara M Paravicini
JOURNAL OF CELLULAR PHYSIOLOGY | WILEY | Published : 2021
Epidermal growth factor (EGF) receptors (ErbB1-ErbB4) promote cardiac development and growth, although the specific EGF ligands and receptor isoforms involved in growth/repair versus pathology remain undefined. We challenged ventricular cardiomyocytes with EGF-like ligands and observed that selective activation of ErbB4 (the receptor for neuregulin 1 [NRG1]), but not ErbB1 (the receptor for EGF, EGFR), stimulated hypertrophy. This lack of direct ErbB1-mediated hypertrophy occurred despite robust activation of extracellular-regulated kinase 1/2 (ERK) and protein kinase B. Hypertrophic responses to NRG1 were unaffected by the tyrosine kinase inhibitor (AG1478) at concentrations that are select..View full abstract
Awarded by National Health and Medical Research Council of Australia
The authors thank Dr. Mona Nemer (University of Ottawa) for kindly providing the hypertrophic gene promoter luciferase reporter plasmids (MLC-2V, ANP-328, and cyclin D), Dr. Andrew Dunbar (formerly of GroPep Limited) for bovine betacelluin, Professor David Riese II (Auburn University) for neuregulin isoforms -2 alpha, -2 beta, -3 and -4, and Mr. James Goonan for constructing the short hairpin RNA plasmids for ErbB2 and ErbB4. The authors also gratefully acknowledge cardiac tissue provided by Professor Karen Moritz (University of Queensland). Contract grant sponsor National Health and Medical Research Council of Australia; Contract grant numbers 1024726 and 1085996 to Walter G. Thomas funded this study.