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ERK regulation upon contact inhibition in fibroblasts

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Abstract

Despite the understanding of the importance of mitogen-activated protein (MAP) kinase activation in the stimulation of growth, little is known about the role of MAP kinase regulation during contact inhibited growth control. To investigate the role of the MAP kinase extracellular signal-regulated kinase (ERK) during the transition to a contact inhibited state, cultures of normal fibroblasts (BJ) were grown to different stages of confluency. The levels of MAP kinase phosphatase (MKP) expression and the amount of active ERK and MAP ERK kinase (MEK) in these cultures were assessed through western blot analysis and were compared to fibrosarcoma cell cultures (HT-1080), which lack contact inhibition. In normal fibroblasts, the amounts of active MEK and ERK decline at contact inhibition, concurrently with a rise in MKP-1, MKP-2, and MKP-3 protein levels. In contrast, fibrosarcoma cells appear to lack density-dependent regulation of the ERK pathway. Additionally, altering the redox environment of fibrosarcoma cells to a less reducing state, as seen during contact inhibition, results in increased MKP-1 expression. Taken together, these results suggest that the altered redox environment upon contact inhibition may contribute to the regulation of ERK inactivation by MKPs.

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Authors and Affiliations

  1. Department of Biology, Monmouth University, West Long Branch, 07764, NJ, USA

    Joshua Wayne, Jennifer Sielski, Ahmed Rizvi, Ketleine Georges & Dorothy Hutter

  2. Department of Biology, Monmouth University, 400 Cedar Avenue, West Long Branch, 07764, NJ, USA

    Dorothy Hutter

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  1. Joshua Wayne
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  2. Jennifer Sielski
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Correspondence to Dorothy Hutter.

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Wayne, J., Sielski, J., Rizvi, A. et al. ERK regulation upon contact inhibition in fibroblasts. Mol Cell Biochem 286, 181–189 (2006). https://doi.org/10.1007/s11010-005-9089-z

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  • DOI: https://doi.org/10.1007/s11010-005-9089-z

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