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Calreticulin enhances B2 bradykinin receptor maturation and heterodimerization


Abd Alla, J; Reeck, K; Langer, A; Streichert, T; Quitterer, U (2009). Calreticulin enhances B2 bradykinin receptor maturation and heterodimerization. Biochemical and Biophysical Research Communications (BBRC), 387(1):186-190.

Abstract

In different native tissues and cells the receptor for the vasodepressor bradykinin, B(2), forms dimers with the receptor for the vasopressor angiotensin II, AT(1). Because AT(1)/B(2) heterodimers may contribute to enhanced angiotensin II-stimulated signaling under pathophysiological conditions, we analyzed mechanisms of AT(1)/B(2) heterodimerization. We found that efficient B(2) receptor maturation was a prerequisite for heterodimerization because only the fully mature B(2) receptor was capable to interact with AT(1). To identify chaperones involved in B(2) receptor maturation and heterodimerization we performed microarray gene expression profiling of human embryonic kidney (HEK293) cells. The expression of the chaperone calreticulin was up-regulated in cells with efficient B(2) receptor maturation. Vice versa, upon down regulation of calreticulin expression by RNA interference, B(2) receptor maturation and AT(1)/B(2) receptor heterodimerization were significantly impaired. Concomitantly, the B(2) receptor-mediated enhancement of AT(1)-stimulated signaling was reduced. Thus, calreticulin enhances B(2) receptor maturation and heterodimerization with AT(1).

In different native tissues and cells the receptor for the vasodepressor bradykinin, B(2), forms dimers with the receptor for the vasopressor angiotensin II, AT(1). Because AT(1)/B(2) heterodimers may contribute to enhanced angiotensin II-stimulated signaling under pathophysiological conditions, we analyzed mechanisms of AT(1)/B(2) heterodimerization. We found that efficient B(2) receptor maturation was a prerequisite for heterodimerization because only the fully mature B(2) receptor was capable to interact with AT(1). To identify chaperones involved in B(2) receptor maturation and heterodimerization we performed microarray gene expression profiling of human embryonic kidney (HEK293) cells. The expression of the chaperone calreticulin was up-regulated in cells with efficient B(2) receptor maturation. Vice versa, upon down regulation of calreticulin expression by RNA interference, B(2) receptor maturation and AT(1)/B(2) receptor heterodimerization were significantly impaired. Concomitantly, the B(2) receptor-mediated enhancement of AT(1)-stimulated signaling was reduced. Thus, calreticulin enhances B(2) receptor maturation and heterodimerization with AT(1).

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1 citation in Web of Science®
12 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:02 Dec 2009 15:16
Last Modified:05 Apr 2016 13:36
Publisher:Elsevier
ISSN:0006-291X
Funders:SNF
Publisher DOI:https://doi.org/10.1016/j.bbrc.2009.07.011
PubMed ID:19580784
Permanent URL: https://doi.org/10.5167/uzh-25081

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