PMID: 15228089Jul 2, 2004Paper

Glucose-induced binding of the polypyrimidine tract-binding protein (PTB) to the 3'-untranslated region of the insulin mRNA (ins-PRS) is inhibited by rapamycin

Molecular and Cellular Biochemistry
Linda Tillmar, Nils Welsh

Abstract

Despite considerable knowledge on the regulation of insulin gene transcription, little is known about the post-transcriptional control mechanisms of this gene. We have recently reported glucose- and hypoxia-regulated binding of the polypyrimidine tract-binding protein (PTB) to the pyrimidine-rich sequence of the 3'-untranslated insulin mRNA (ins-PRS), an event which may control insulin mRNA stability. The present aim was to probe for the signaling pathways that control this binding activity. Rat islets were exposed to pharmacological inhibitors against several molecules, previously shown to be involved in glucose signaling. The inhibitors used were; LY 294002 (PI3 kinase), Rp-cAMP triatylamine (the cAMP-dependent protein kinase PKA), bisindolylmaleimide I hydrochloride (PKC), PD 098059 (ERK1/ERK2), SB 203580 (p38/SAPK2a), rapamycin (mTOR) and okadaic acid (PP1/2A). PTB-binding activity to the ins-PRS was then analyzed by elecrophoretic mobility shift assay (EMSA). The glucose-induced PTB-binding was only inhibited by the mTOR inhibitor rapamycin. Rapamycin also reduced glucose-induced insulin mRNA expression. Thus, our results suggest an involvement of mTOR in glucose-induced PTB/ins-PRS binding and insulin mRNA stability.

Citations

Jul 18, 2008·Biochemical Society Transactions·Kirsty SawickaAnne E Willis
Aug 12, 2009·Molecular and Cellular Biology·Ivan BabicDouglas L Black
Jul 9, 2009·Journal of Cellular and Molecular Medicine·Kiyoshi MasudaMyriam Gorospe
Aug 6, 2005·IUBMB Life·Alberto Pugliese
Nov 18, 2008·Nucleic Acids Research·Kyung-Chul WooKyong-Tai Kim
Aug 19, 2015·Journal of Experimental Botany·Sung Ki ChoDavid J Hannapel
Jan 27, 2005·Biochemical and Biophysical Research Communications·Rikard G Fred, Nils Welsh
Apr 3, 2007·Biochimica Et Biophysica Acta·Shumei MaJiuyong Xie

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