@article{Lebrun2000adhes-7657,
  year={2000},
  doi={10.1074/jbc.M006162200},
  title={Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression},
  number={49},
  volume={275},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={38371--38377},
  author={Lebrun, Patricia and Baron, Véronique and Hauck, Christof R. and Schlaepfer, David D. and Obberghen, Emmanuel van}
}

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    <dc:contributor>Baron, Véronique</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:36:07Z</dc:date>
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    <dc:creator>Hauck, Christof R.</dc:creator>
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    <dc:creator>Schlaepfer, David D.</dc:creator>
    <dcterms:abstract xml:lang="deu">bIntegrins are transmembrane receptors involved in interactions between cells and extracellular matrix proteins. Here we show that cell adhesion regulates insulin receptor substrate-1 (IRS-1) mRNA synthesis. When fibroblasts are held in suspension, lower levels of IRS-1 mRNA, but not of IRS-2 mRNA, are detected, and this effect is due to the negative regulation of IRS-1 transcription rather than to decreased mRNA stability. Upon fibronectin- or vitronectin-mediated integrin stimulation, the level of IRS-1 mRNA was restored within 4 h. The focal adhesion kinase (FAK) is known to be activated upon integrin stimulation, and we found that IRS-1 was not expressed in FAK-/- cells. Stable re-expression of epitope-tagged FAK in FAK-/- fibroblasts (DA2 cells) restored normal levels of IRS-1 expression, confirming that IRS-1 mRNA expression is regulated by FAK. It is known that integrins activate the JNK pathway. However, in adherent FAK-/- cells, we failed to detect activation of JNK, whereas JNK was stimulated in DA2 cells. This confirms the role of FAK in integrin-induced JNK stimulation. FAK-independent stimulation of JNK with anisomycin treatment both in FAK-/- cells and in suspended FAK+/+ cells confirmed that IRS-1 mRNA transcription can be partially regulated by JNK. We suggest that integrins can modulate insulin and insulin-like growth factor-1 signaling pathways by regulating the levels of IRS-1 in cells and that FAK-mediated signaling to JNK is one pathway involved in this process.</dcterms:abstract>
    <dc:contributor>Hauck, Christof R.</dc:contributor>
    <dcterms:title>Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression</dcterms:title>
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    <dc:contributor>Lebrun, Patricia</dc:contributor>
    <dc:creator>Lebrun, Patricia</dc:creator>
    <dcterms:issued>2000</dcterms:issued>
    <dc:contributor>Schlaepfer, David D.</dc:contributor>
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    <dc:contributor>Obberghen, Emmanuel van</dc:contributor>
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    <dc:creator>Obberghen, Emmanuel van</dc:creator>
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    <dcterms:bibliographicCitation>First publ. in: Journal of Biological Chemistry 275 (2000), 49, pp. 38371 38377</dcterms:bibliographicCitation>
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