Transforming growth factor-β-induced expression of the apolipoprotein e gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2

Singh, Nishi N. and Ramji, Dipak Purshottam ORCID: https://orcid.org/0000-0002-6419-5578 2006. Transforming growth factor-β-induced expression of the apolipoprotein e gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2. Arteriosclerosis Thrombosis and Vascular Biology 26 (6) , pp. 1323-1329. 10.1161/01.ATV.0000220383.19192.55

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Abstract

Objective— The cytokine transforming growth factor-β (TGF-β) and apolipoprotein E (apoE) play potent antiatherogenic roles. Despite such importance, the mechanisms underlying the regulation of apoE expression by TGF-β have not been characterized and were therefore investigated. Methods and Results— Using THP-1 cell line as a model system, with key findings confirmed in primary cultures, we show that TGF-β induces the expression of apoE, and this is prevented by pharmacological inhibitors of c-Jun N-terminal kinase (JNK), p38 kinase, and casein kinase 2 (CK2). In support for an important role for these pathways, TGF-β activates JNK, p38 kinase, and CK2, and dominant-negative (DN) forms of these proteins inhibit the cytokine-induced apoE expression. TGF-β also increases the phosphorylation and expression of c-Jun, a downstream target for JNK action and a component of activator protein-1 (AP-1), and DN c-Jun inhibits the induction of apoE expression in response to the cytokine. AP-1 DNA binding was also induced by TGF-β, and the action of p38 kinase, JNK, and CK2 converged on the activation of c-Jun/AP-1. Conclusions— These studies reveal a novel role for JNK, p38 kinase, CK2, and c-Jun/AP-1 in the TGF-β–induced expression of apoE.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	Apolipoprotein E; atherosclerosis; macrophage; TGF-β; signal transduction.
Publisher:	American Heart Association, Inc.
ISSN:	1079-5642
Last Modified:	27 Oct 2022 08:48
URI:	https://orca.cardiff.ac.uk/id/eprint/63440

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