Article abstract
Nature Cell Biology 8, 435 - 445 (2006)
Published online: 16 April 2006 | doi:10.1038/ncb1395
Synergy of glucose and growth hormone signalling in islet cells through ICA512 and STAT5
Hassan Mziaut1, Mirko Trajkovski1, Stephan Kersting1,2, Armin Ehninger1, Anke Altkrüger1, Régis P. Lemaitre4, Darja Schmidt5, Hans-Detlev Saeger2, Myung-Shik Lee6, David N. Drechsel4, Stefan Müller5 & Michele Solimena1,3
Abstract
Nutrients and growth hormones promote insulin production and the proliferation of pancreatic 
-cells. An imbalance between ever-increasing metabolic demands and insulin output causes diabetes. Recent evidence indicates that -cells enhance insulin gene expression depending on their secretory activity. This signalling pathway involves a catalytically inactive receptor tyrosine phosphatase, ICA512, whose cytoplasmic tail is cleaved on glucose-stimulated exocytosis of insulin secretory granules and then moves into the nucleus, where it upregulates insulin transcription. Here, we show that the cleaved cytosolic fragment of ICA512 enhances the transcription of secretory granule genes (including its own gene) by binding to tyrosine phosphorylated signal transducers and activators of transcription (STAT) 5 and preventing its dephosphorylation. Sumoylation of ICA512 by the E3 SUMO ligase PIASy, in turn, may reverse this process by decreasing the binding of ICA512 to STAT5. These findings illustrate how the exocytosis of secretory granules, through a retrograde pathway that sustains STAT activity, converges with growth hormone signalling to induce adaptive changes in -cells in response to metabolic demands.
- Experimental Diabetology, School of Medicine, Dresden University of Technology, Dresden 01307, Germany.
- Department of Surgery, School of Medicine, Dresden University of Technology, Dresden 01307, Germany.
- Medical Clinic III, School of Medicine, Dresden University of Technology, Dresden 01307, Germany.
- Max Planck Institute for Molecular Cell Biology and Genetics, Dresden 01307, Germany.
- Max Planck Institute for Biochemistry, Martinsried 82152, Germany.
- Department of Medicine, Samsung Medical Center, Sungkyunkwan Univ. School of Medicine, Seoul 135–710, Korea.
Correspondence to: Michele Solimena1,3 e-mail: michele.solimena@mailbox.tu-dresden.de
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