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Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

Sung, H.Y., Guan, H.T., Czibula, A., King, A.R., Eder, K., Heath, E., Suvarna, S.K., Dower, S.K., Wilson, A.G., Francis, S.E., Crossman, D.C. and Kiss-Toth, E. (2007) Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways. Journal of Biological Chemistry, 282 (25). pp. 18379-18387. ISSN 1083-351X


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Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood.

Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2007 by the American Society for Biochemistry and Molecular Biology. This is an author produced version of a paper published in Journal of Biolgical Chemistry. Uploaded in accordance with the publisher's self-archiving policy.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Clinical Sciences Division North (Sheffield)
Depositing User: Sherpa Assistant
Date Deposited: 31 Aug 2007 13:30
Last Modified: 08 Feb 2013 16:54
Published Version: http://dx.doi.org/10.1074/jbc.M610792200
Status: Published
Publisher: Amerian Society for Biochemistry Molecular Biology Inc.
Refereed: Yes
Identification Number: 10.1074/jbc.M610792200
URI: http://eprints.whiterose.ac.uk/id/eprint/2659

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