Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System

Abstract

Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications.

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

“…In recent years, the EGFR signaling pathway has been reported to be impaired in several neurometabolic conditions such as diabetes [25], hypertension [26], schizophrenia [27], AD [28], gliomas [29], Parkinson disease [30], and cardiovascular functions [31]. EGFR is expressed in several brain regions involved in memory, neuronal survival, and regeneration [32].…”

Rapid Renal Regulation of Peroxisome Proliferator-activated Receptor γ Coactivator-1α by Extracellular Signal-Regulated Kinase 1/2 in Physiological and Pathological Conditions

“…DECEMBER 23, 2016 • VOLUME 291 • NUMBER 52 include EGFR ligands, TGF␣ and HB-EGF (heparin-binding EGF-like growth factor), and/or transactivation pathways (ADAM17, ANGII (angiotensin II), TWEAK/Fn14) (4,40).…”

“…Raf phosphorylates MEK1/2, which phosphorylates ERK1/2. ERK1/2 is thought to be the only substrate for MEK1/2 phosphorylation, which has allowed for MEK1/2 inhibitors to be used specifically for ERK1/2 inactivation (3,4). ERK1/2 is also activated by cell stressors, including reactive oxygen species.…”

AT1 receptor signaling pathways in the cardiovascular system

“…The AT1 receptor is predominantly expressed in various tissues throughout the cardiovascular system including vascular smooth muscle, endothelium, heart and kidney. The AT1 receptor promotes intracellular signaling pathways through the activation of various protein kinases, subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, growth factor receptor transactivation (1–5), or direct interactions with AT1 receptor interacting proteins such as Janus kinase 2 (JAK2), phospholipase C (PLC) γ1, AT1 receptor associated protein (ATRAP), type 1 angiotensin II receptor-associated protein (ARAP1) and Guanine nucleotide exchange factor (GEF)-like protein (GLP) (1, 2, 6, 7). …”