Hijacking epidermal growth factor receptors by angiotensin II: New possibilities for understanding and treating cardiac hypertrophy

Smith N. J., Chan, H.-W., Osborne, J. E., Thomas, W. G. and Hannan, R. D. (2004) Hijacking epidermal growth factor receptors by angiotensin II: New possibilities for understanding and treating cardiac hypertrophy. Cellular and Molecular Life Sciences, 61 21: 2695-2703. doi:10.1007/s00018-004-4244-3


Author Smith N. J.
Chan, H.-W.
Osborne, J. E.
Thomas, W. G.
Hannan, R. D.
Title Hijacking epidermal growth factor receptors by angiotensin II: New possibilities for understanding and treating cardiac hypertrophy
Journal name Cellular and Molecular Life Sciences   Check publisher's open access policy
ISSN 1420-682X
1420-9071
1023-294X
Publication date 2004-11-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s00018-004-4244-3
Volume 61
Issue 21
Start page 2695
End page 2703
Total pages 9
Place of publication Basel, Switzerland
Publisher Birkhauser
Language eng
Subject 060110 Receptors and Membrane Biology
060111 Signal Transduction
060199 Biochemistry and Cell Biology not elsewhere classified
060108 Protein Trafficking
060602 Animal Physiology - Cell
110201 Cardiology (incl. Cardiovascular Diseases)
110903 Central Nervous System
Formatted abstract
Activation of the type 1 angiotensin II receptor (AT1R) is associated with the aetiology of left ventricular hypertrophy, although the exact intracellular signalling mechanism(s) remain unclear. Transactivation of the epidermal growth factor receptor (EGFR) has emerged as a central mechanism by which the G protein-coupled AT1R, which lacks intrinsic tyrosine kinase activity, can stimulate the mitogen-activated protein kinase signalling pathways thought to mediate cardiac hypertrophy. Current studies support a model whereby AT1R-dependent transactivation of EGFRs on cardiomyocytes involves stimulation of membrane-bound metalloproteases, which in turn cleave EGFR ligands such as heparin-binding EGF from a plasma membrane-associated precursor. Numerous aspects of the ‘triple membrane-passing signalling’ paradigm of AT1R-induced EGFR transactivation remain to be characterised, including the identity of the specific metalloproteases involved, the intracellular mechanism for their activation and the exact EGFR subtypes required. Here we examine how ‘hijacking’ of the EGFR might explain the ability of the AT1R to elicit the temporally and qualitatively diverse responses characteristic of the hypertrophic phenotype, and discuss the ramifications of delineating these pathways for the development of new therapeutic strategies to combat cardiac hypertrophy.
© Birkhäuser Verlag, Basel, 2004
Keyword Type 1 angiotensin II receptor (AT1R)
Transactivation
EGFR - metalloprotease
HB-EGF
Cardiac hypertrophy
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