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Signal transduction of angiotensin II type 1 receptor through receptor tyrosine kinase
1Department of Biochemistry, Vanderbilt University School of Medicine, 37232, Nashville, TN 37232, USA. satoru.eguchi@vanderbilt.edu
Abstract:
In cultured vascular smooth muscle cells, the angiotensin II (AngII) type-1 (AT(1)) receptor generates growth-promoting signals via the epidermal growth factor (EGF) receptor system. This 'transactivation' mechanism now appears to be utilized by a variety of G-protein-coupled receptors in many cells. The AngII-induced EGF receptor transactivation leads to activation of downstream signaling molecules including Ras, ERK, c-fos, Akt/protein kinase B, and p70 S6 kinase. We propose three possible mechanisms may be involved in the transactivation, (i) an upstream tyrosine kinase, (ii) reactive oxygen species, and (iii) a juxtacrine activation of the EGF receptor ligand. Whether the EGF receptor signal transduction induced by AngII plays an essential role in cardiovascular remodeling remains to be investigated.
Insights
Angiotensin II (AngII) activates vascular smooth muscle cell growth through the epidermal growth factor (EGF) receptor system. This transactivation involves key signaling molecules and may be crucial for cardiovascular remodeling.
Area of Science:
- Cellular signaling pathways
- Vascular biology
- Receptor transactivation
Background:
- The angiotensin II (AngII) type-1 (AT(1)) receptor is known to promote cell growth in vascular smooth muscle cells.
- Epidermal growth factor (EGF) receptor signaling is a critical pathway in cellular processes.
- G-protein-coupled receptors (GPCRs) utilize diverse signaling mechanisms.
Purpose of the Study:
- To investigate the mechanism of AngII-induced growth signaling in vascular smooth muscle cells.
- To elucidate the role of epidermal growth factor (EGF) receptor transactivation in AngII signaling.
- To identify potential mechanisms underlying EGF receptor transactivation by AngII.
Main Methods:
- Utilized cultured vascular smooth muscle cells.
- Investigated AngII-induced activation of downstream signaling molecules.
- Proposed potential mechanisms for EGF receptor transactivation.
Main Results:
- Angiotensin II (AngII) type-1 (AT(1)) receptor signaling activates epidermal growth factor (EGF) receptor, a process termed transactivation.
- This transactivation leads to the activation of downstream signaling pathways including Ras, ERK, c-fos, Akt/protein kinase B, and p70 S6 kinase.
- Three potential mechanisms for transactivation were proposed: tyrosine kinase, reactive oxygen species, and juxtacrine ligand activation.
Conclusions:
- Angiotensin II (AngII) utilizes the epidermal growth factor (EGF) receptor system for growth promotion in vascular smooth muscle cells.
- The precise role of AngII-induced EGF receptor signal transduction in cardiovascular remodeling requires further investigation.