http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Synergy of glucose and growth hormone signalling in islet cells through ICA512 and STAT5
Mziaut, Hassan,Trajkovski, Mirko,Kersting, Stephan,Ehninger, Armin,Altkrü,ger, Anke,Lemaitre, Ré,gis P.,Schmidt, Darja,Saeger, Hans-Detlev,Lee, Myung-Shik,Drechsel, David N.,Mü,ller, Ste Nature Publishing Group 2006 Nature cell biology Vol.8 No.5
Nutrients and growth hormones promote insulin production and the proliferation of pancreatic β-cells. An imbalance between ever-increasing metabolic demands and insulin output causes diabetes. Recent evidence indicates that β-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 β-cells in response to metabolic demands.