Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal integration of metabolic signals in pancreatic ß cells Dominique A. Glauser and Werner Schlegel 1 Fondation pour Recherches Médicales, University of Geneva, Switzerland 1 Correspondence: Fondation pour Recherches Médicales, Av. de la Roseraie 64, 1211 Geneva, Switzerland. E-mail: werner.schlegel@medecine.unige.ch The AP-1 transcription factor composed of fos and jun gene products mediates transcriptional responses to hormonal and metabolic stimulations of pancreatic beta cells. Here, we investigated the mechanisms that dynamically control expression of AP-1 subunit proteins. In MIN6 cells, glucose and GLP-1 raised c-FOS protein with biphasic kinetics, an initial peak being followed by a plateau that persisted as long as stimuli were maintained. ERK1/2 activation paralleled c-FOS expression. Whereas initial induction of c-FOS protein required ERK1/2-dependent activation of c -fos transcription and de novo protein synthesis, persistent accumulation of c-FOS under sustained stimulation did not. Indeed, dependent on ERK1/2 activation, c-FOS accumulated in its hyperphosphorylated form protected from degradation through the proteasome pathway. The implication of ERK1/2 in the accumulation of c-FOS protein was confirmed in rat primary ß cells, and the functional consequences of this mechanism were demonstrated with DNA-binding and reporter assays. Altogether these findings reveal a sequential regulation of AP-1 by ERK1/2, which initially increases transcription of c- fos and, if stimulation persists, stabilizes freshly synthesized c-FOS protein to efficiently activate the transcription of AP-1-regulated genes. This ERK1/2-AP-1 module can function as a temporal integrator converting metabolic stimuli of different durations into differential transcriptional outputs.—Glauser, D. A., Schlegel, W. Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal integration of metabolic signals in pancreatic ß cells. Key Words: Langerhans islets • c-fos • protein stability • proteolysis
End of preview. The entire article is 10 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/sequential-actions-of-erk1-2-on-the-ap-1-transcription-factor-allow-1POuDOMh7F
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal integration of metabolic signals in pancreatic ß cells
Glauser, Dominique A.; Schlegel, Werner
Follow The FASEB Journal
, Volume 21 (12): 3240
Fed of American Socs for Experimental Biology – Oct 1, 2007
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
