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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2006     Display Documents

ID: 311187.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2006
Synergy of glucose and growth hormone signalling in islet cells through ICA512 and STAT5
Authors:Mziaut, Hassan; Trajkovski, Mirko; Kersting, Stephan; Ehninger, Armin; Altkruger, Anke; Lemaitre, Regis P; Schmidt, Darja; Saeger, Hans-Detlev; Lee, Myung-Shik; Drechsel, David N; Muller, Stefan; Solimena, Michele
Date of Publication (YYYY-MM-DD):2006
Title of Journal:Nature Cell Biology
Issue / Number:5
Start Page:435
End Page:445
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Nutrients and growth hormones promote insulin production and the proliferation of pancreatic beta-cells. An imbalance between ever-increasing metabolic demands and insulin output causes diabetes. Recent evidence indicates that beta-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 beta-cells in response to metabolic demands.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für molekulare Zellbiologie und Genetik
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