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(Circulation Research. 2006;99:455.)
© 2006 American Heart Association, Inc.

Editorials

Inflame My Heart (by p38-MAPK)

Angela Clerk, Peter H. Sugden

From the National Heart and Lung Institute (NHLI) Division (Cardiac Medicine), Faculty of Medicine, Imperial College London, London, UK

Correspondence to Angela Clerk PhD, NHLI Division (Cardiac Medicine), Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK. E-mail a.clerk@imperial.ac.uk

See related article, pages 485–493

Key Words: intracellular signalling • mitogen-activated protein kinases • gene expression profiling • cardiac pathology

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Although many studies have explored the stimuli which promote hypertrophic growth or death in cardiac myocytes and the signaling pathways which they activate, the mechanisms by which these pathways promote the pathophysiological responses are still obscure. The mitogen-activated protein kinase (MAPK) cascades (in which MAPKs are phosphorylated and activated by upstream MAPK kinases [MKKs] which are, in turn, phosphorylated and activated by MKK kinases [MKKKs]) were identified in the early- to mid-1990s as potentially key regulatory pathways in cardiac myocyte pathophysiology.^1,2 The principal MAPKs investigated in cardiac myocytes are the extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38-MAPKs. ERK1/2 are potently activated by hypertrophic stimuli, whereas JNKs and p38-MAPKs are potently activated by cellular stresses (eg, oxidative stress). However, there is cross-talk such that JNKs and p38-MAPKs are activated by hypertrophic stimuli and ERK1/2 are activated by cellular stresses, and the contribution of each pathway to the overall cardiac myocyte response is not entirely clear.

MAPKs phosphorylate a number of known transcription factors to alter their transactivating activities thus, presumably, influencing gene expression to elicit the cellular response.³ Nevertheless, the immediate consequences (ie, the transcription factors which are phosphorylated) and downstream consequences (ie, genes with altered expression) of MAPK signaling in the heart or specifically in cardiac myocytes are still largely unknown. To start to address this issue for the p38-MAPK pathway in the (rat) heart (Figure), Tenhunen et al⁴ directly injected adenoviruses encoding wild-type (WT) p38-MAPK together with a mutated constitutively-activated (CA) upstream kinase . . . [Full Text of this Article]

Related Article:

Identification of Cell Cycle Regulatory and Inflammatory Genes As Predominant Targets of p38 Mitogen-Activated Protein Kinase in the Heart

Olli Tenhunen, Jaana Rysä, Mika Ilves, Ylermi Soini, Heikki Ruskoaho, and Hanna Leskinen
Circ. Res. 2006 99: 485-493. [Abstract] [Full Text] [PDF]

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