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

Youn Sung Hye, Hongtao Guan, A. Czibula, Andrea R. King, Katalin Eder, Emily Heath, Kim Suvarna, Steven K. Dower, Anthony G. Wilson, Sheila E. Francis, David C. Crossman, Endre Kiss-Toth

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Abstract

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, although 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, whereas the activation and the expression of MKK4/SEK1 are not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries when compared with non-atherosclerotic controls, suggesting that this protein may play 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.

Original languageEnglish
Pages (from-to)18379-18387
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
Publication statusPublished - Jun 22 2007

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Chemotaxis
Mitogen-Activated Protein Kinases
Smooth Muscle Myocytes
Muscle
Vascular Smooth Muscle
Cells
Phosphotransferases
Chemical activation
Cell proliferation
Cell Proliferation
Cytology
Physiological Phenomena
Pathologic Processes
Wound Healing
Modulators
Cell Movement
Cell Biology
Arteries
Proteins

ASJC Scopus subject areas

  • Biochemistry

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Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways. / Hye, Youn Sung; Guan, Hongtao; Czibula, A.; King, Andrea R.; Eder, Katalin; Heath, Emily; Suvarna, Kim; Dower, Steven K.; Wilson, Anthony G.; Francis, Sheila E.; Crossman, David C.; Kiss-Toth, Endre.

In: Journal of Biological Chemistry, Vol. 282, No. 25, 22.06.2007, p. 18379-18387.

Research output: Contribution to journalArticle

Hye, YS, Guan, H, Czibula, A, King, AR, Eder, K, Heath, E, Suvarna, K, Dower, SK, Wilson, AG, Francis, SE, Crossman, DC & Kiss-Toth, E 2007, 'Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways', Journal of Biological Chemistry, vol. 282, no. 25, pp. 18379-18387. https://doi.org/10.1074/jbc.M610792200
Hye, Youn Sung ; Guan, Hongtao ; Czibula, A. ; King, Andrea R. ; Eder, Katalin ; Heath, Emily ; Suvarna, Kim ; Dower, Steven K. ; Wilson, Anthony G. ; Francis, Sheila E. ; Crossman, David C. ; Kiss-Toth, Endre. / Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 25. pp. 18379-18387.
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