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Endothelin A and endothelin B receptors differ in their ability to stimulate ERK1/2 activation

Item Type:Article
Title:Endothelin A and endothelin B receptors differ in their ability to stimulate ERK1/2 activation
Creators Name:Grantcharova, E., Reusch, H.P., Beyermann, M., Rosenthal, W. and Oksche, A.
Abstract:Endothelin-1 (ET-1) acts on two different G protein-coupled receptors, namely the endothelin A (ET(A)) and the endothelin B (ET(B)) receptors. Both receptor subtypes show differences in their tissue expression and signal transduction. In the present study, we compared the ability of ET(A) and ET(B) receptors to stimulate extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, we analyzed the role of the extracellular N terminus for ERK1/2 activation, because the ET(B) receptor undergoes an agonist-dependent N-terminal proteolysis. ET-1 stimulation of HEK293 cells stably expressing the ET(A) receptor induced a monophasic, but sustained ERK1/2 activation, whereas the ET(B) receptor showed a biphasic ERK1/2 activation. A truncated mutant ET(B) receptor, lacking the proteolytically cleaved N terminus (delta2-64 ET(B)) revealed only a monophasic and transient ERK1/2 activation. Treatment of HEK293 delta2-64 ET(B) cell clones with ET-1 and a synthetic NT27-64 peptide, corresponding to the N-terminally cleaved fragment of the ET(B) receptor and ET-1, did not restore the biphasic activation of ERK1/2. A chimeric ET(B) receptor in which the N terminus was replaced by the N terminus of the ET(A) receptor elicited biphasic ERK1/2 activation. The presented data suggest that an intact N terminus of the ET(B) receptor is necessary for the second phase of ERK1/2 activation. However, it appears that the length of the N terminus rather than a specific sequence motif is required for biphasic ERK1/2 activation.
Keywords:Endothelin, Glycosylation, G protein-coupled receptor, MAPK
Source:Experimental Biology and Medicine
Publisher:Society for Experimental Biology and Medicine
Page Range:757-760
Date:June 2006
Official Publication:http://www.ebmonline.org/cgi/content/abstract/231/6/757
PubMed:View item in PubMed

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