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  Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion

Sacco, F., Humphrey, S. J., Cox, J., Mischnik, M., Schulte, A., Klabunde, T., et al. (2016). Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nature Communications, 7: 13250. doi:10.1038/ncomms13250.

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Sacco, Francesca1, Autor           
Humphrey, Sean J.1, Autor           
Cox, Jürgen2, Autor           
Mischnik, Marcel3, Autor
Schulte, Anke3, Autor
Klabunde, Thomas3, Autor
Schaefer, Matthias3, Autor
Mann, Matthias1, Autor           
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_2063284              
3external, ou_persistent22              

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Schlagwörter: PANCREATIC BETA-CELLS; IN-VIVO; SIGNALING NETWORKS; MASS-SPECTROMETRY; PROTEIN-KINASES; COPY-NUMBER; PHOSPHORYLATION; DYNAMICS; COMPLEX; MOUSEScience & Technology - Other Topics;
 Zusammenfassung: Insulin-secreting beta cells play an essential role in maintaining physiological blood glucose levels, and their dysfunction leads to the development of diabetes. To elucidate the signalling events regulating insulin secretion, we applied a recently developed phosphoproteomics workflow. We quantified the time-resolved phosphoproteome of murine pancreatic cells following their exposure to glucose and in combination with small molecule compounds that promote insulin secretion. The quantitative phosphoproteome of 30,000 sites clustered into three main groups in concordance with the modulation of the three key kinases: PKA, PKC and CK2A. A high-resolution time course revealed key novel regulatory sites, revealing the importance of methyltransferase DNMT3A phosphorylation in the glucose response. Remarkably a significant proportion of these novel regulatory sites is significantly down-regulated in diabetic islets. Control of insulin secretion is embedded in an unexpectedly broad and complex range of cellular functions, which are perturbed by drugs in multiple ways.

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Sprache(n): eng - English
 Datum: 2016-11-14
 Publikationsstatus: Online veröffentlicht
 Seiten: 13
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000387558800001
DOI: 10.1038/ncomms13250
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Titel: Nature Communications
  Kurztitel : Nat. Commun.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: London : Nature Publishing Group
Seiten: - Band / Heft: 7 Artikelnummer: 13250 Start- / Endseite: - Identifikator: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723