Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. / Sacco, Francesca; Humphrey, Sean J; Cox, Jürgen; Mischnik, Marcel; Schulte, Anke; Klabunde, Thomas; Schäfer, Matthias; Mann, Matthias.
In: Nature Communications, Vol. 7, 14.11.2016, p. 13250.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion
AU - Sacco, Francesca
AU - Humphrey, Sean J
AU - Cox, Jürgen
AU - Mischnik, Marcel
AU - Schulte, Anke
AU - Klabunde, Thomas
AU - Schäfer, Matthias
AU - Mann, Matthias
PY - 2016/11/14
Y1 - 2016/11/14
N2 - 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 downregulated 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.
AB - 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 downregulated 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.
KW - Journal Article
U2 - 10.1038/ncomms13250
DO - 10.1038/ncomms13250
M3 - Journal article
C2 - 27841257
VL - 7
SP - 13250
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -
ID: 184324149