Publikation: Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
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.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
LEBRUN, Patricia, Véronique BARON, Christof R. HAUCK, David D. SCHLAEPFER, Emmanuel van OBBERGHEN, 2000. Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression. In: Journal of Biological Chemistry. 2000, 275(49), pp. 38371-38377. ISSN 0021-9258. Available under: doi: 10.1074/jbc.M006162200BibTex
@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} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/7657"> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:36:07Z</dcterms:available> <dc:contributor>Baron, Véronique</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:36:07Z</dc:date> <dc:format>application/pdf</dc:format> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/2.0/"/> <dc:creator>Hauck, Christof R.</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <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> <dc:rights>Attribution-NonCommercial-NoDerivs 2.0 Generic</dc:rights> <dc:contributor>Lebrun, Patricia</dc:contributor> <dc:creator>Lebrun, Patricia</dc:creator> <dcterms:issued>2000</dcterms:issued> <dc:contributor>Schlaepfer, David D.</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7657"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7657/1/Cell_adhesion_and_focal_adhesion_kinase_regulate_insulin_receptor_substrate_1_expression.pdf"/> <dc:contributor>Obberghen, Emmanuel van</dc:contributor> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7657/1/Cell_adhesion_and_focal_adhesion_kinase_regulate_insulin_receptor_substrate_1_expression.pdf"/> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dc:creator>Obberghen, Emmanuel van</dc:creator> <dc:creator>Baron, Véronique</dc:creator> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:bibliographicCitation>First publ. in: Journal of Biological Chemistry 275 (2000), 49, pp. 38371 38377</dcterms:bibliographicCitation> <dc:language>eng</dc:language> </rdf:Description> </rdf:RDF>