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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Cdk5 phosphorylates PLD2 to mediate EGF-dependent insulin secretion

Cited 19 times inthomson ciCited 17 times inthomson ci
Title
Cdk5 phosphorylates PLD2 to mediate EGF-dependent insulin secretion
Author
Lee, Hye YoungJung, HyuntaeJang, Il HoSuh, Pann-GhillRyu, Sung Ho
Issue Date
2008-10
Publisher
ELSEVIER SCIENCE INC
Citation
CELLULAR SIGNALLING, v.20, no.10, pp.1787 - 1794
Abstract
Insulin secretion from pancreatic beta-cells is an important process that affects the regulation of glucose level in the blood. In our previous study, we suggested that epidermal growth factor (EGF) stimulates insulin secretion by activating phospholipase D2 (PLD2) [H.Y. Lee, K. Yea, J. Kim, B.D. Lee, Y.C. Chae, H.S. Kim, D.W. Lee, S.H. Kim, J.H. Cho, C.J. Jin, D.S. Koh, K.S. Park, P.G. Suh, S.H. Ryu, 2007. Epidermal Growth Factor Increases Insulin Secretion and Lowers Blood Glucose in Diabetic Mice. J. Cell. Mol. Med. 5:5]. However, the specific mechanism by which PLD2 activation leads to insulin secretion was not determined. In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion. We found that a Cdk5 inhibitor, roscovitine, and dominant-negative Cdk5 inhibited EGF-depenclent PLD2 activation and insulin secretion. EGF stimulation activated Cdk5 activity in rat insulnoma RINm5F cells, and PLD2 phosphorylation by Cdk5 was observed in vitro and in cells. The kinetics of PLD2 phosphorylation correlates with the interaction between PLD2 and Cdk5 and its effect on EGF signaling. We determined that the phosphorylation site of PLD2 was located at Ser(134). PLD2-S134A did not show EGF-dependent phosphorylation and activation by Cdk5. Furthermore, this mutant was unable to mediate EGF-dependent insulin secretion in pancreatic beta cell lines, suggesting that the phosphorylation of PLD2 at Ser(134) by Cdk5 is critical for this process. The study results suggest that PLD2 is a new substrate of Cc1k5 and that the phosphorylation of PLD2 by Cdk5 is involved in EGF-depenclent insulin secretion. (C) 2008 Elsevier Inc. All rights reserved.
URI
https://scholarworks.unist.ac.kr/handle/201301/10097
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=49549116190
DOI
10.1016/j.cellsig.2008.06.009
ISSN
0898-6568
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BIO_Journal Papers
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