N-terminal proteolysis of the endothelin B receptor abolishes its ability to induce EGF receptor transactivation and contractile protein expression in vascular smooth muscle cells

Grantcharova, E.; Reusch, H.P.; Grossmann, S.; Eichhorst, J.; Krell, H.W.; Beyermann, M.; Rosenthal, W.; Oksche, A.

N-terminal proteolysis of the endothelin B receptor abolishes its ability to induce EGF receptor transactivation and contractile protein expression in vascular smooth muscle cells

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Item Type:	Article
Title:	N-terminal proteolysis of the endothelin B receptor abolishes its ability to induce EGF receptor transactivation and contractile protein expression in vascular smooth muscle cells
Creators Name:	Grantcharova, E., Reusch, H.P., Grossmann, S., Eichhorst, J., Krell, H.W., Beyermann, M., Rosenthal, W. and Oksche, A.
Abstract:	OBJECTIVE: The extracellular N terminus of the endothelin B (ETB) receptor is cleaved by a metalloprotease in an agonist-dependent manner, but the physiological role of this N-terminal proteolysis is not known. In this study, we aimed to determine the functional role of the ETB receptor and of its N-terminal cleavage in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMCs expressing either the full-length ETB receptor or an N-terminally truncated ETB receptor (corresponding to the N-terminally cleaved receptor) were analyzed for ligand-induced mitogen-activated protein kinase activation and expression of contractile proteins. In VSMCs expressing the full-length ETB receptor, IRL1620 (an ETB-selective agonist) induced a biphasic extracellular signal-regulated kinase 1/2 (ERK1/2) activation and increased expression of contractile proteins (smooth muscle myosin-1 [SM-1]/SM-2, SM22alpha, and alpha-actin). Interestingly, the second phase of ERK1/2 activation required metalloprotease activity, epidermal growth factor (EGF) receptor transactivation, and predominantly activation of Gi proteins. In contrast, in VSMCs expressing N-terminally truncated ETB receptors, IRL1620 did not elicit EGF transactivation and failed to increase contractile protein expression. CONCLUSIONS: This study is the first to show that stimulation of full-length ETB receptors promotes expression of contractile proteins and may thus participate in the differentiation of VSMCs.
Keywords:	Transactivation, EGF Receptor, ERK1/2, Differentiation, Animals, Rats
Source:	Arteriosclerosis Thrombosis and Vascular Biology
ISSN:	1079-5642
Publisher:	American Heart Association
Volume:	26
Number:	6
Page Range:	1288-1296
Date:	June 2006
Official Publication:	https://doi.org/10.1161/01.ATV.0000220377.51354.30
PubMed:	View item in PubMed

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