Distinct modes of activation of phosphatidylinositol 3-kinase in response to cyclic adenosine 3', 5'-monophosphate or insulin-like growth factor I play different roles in regulation of cyclin D1 and p27Kip1 in FRTL-5 cells

Endocrinology
Toshiaki FukushimaShin-Ichiro Takahashi

Abstract

Bioactivities of IGFs in various cells are often potentiated in the presence of other hormones. In previous studies we showed that pretreatment of rat FRTL-5 thyroid cells with TSH or other cAMP-generating agents markedly potentiated DNA synthesis induced by IGF-I. Under these conditions we found that phosphatidylinositol (PI) 3-kinase was activated in response to either cAMP or IGF stimulus, and both activation modes were indispensable for the potentiation of DNA synthesis. The present studies were undertaken to elucidate how cAMP and/or IGF-I stimulus regulated the G1 cyclin-cyclin dependent kinase (CDK)-inhibitor system, and to determine the roles of PI 3-kinase activation by cAMP or IGF-I stimulus in this system. We found that cAMP pretreatment enhanced IGF-I-dependent increases in cyclin D1, due to synergistic increases in mRNA and elevation of translation rates. Furthermore, cAMP pretreatment enhanced IGF-I-induced protein degradation of the CDK inhibitor, p27(Kip1). These changes well explained an increase in cyclin E, leading to marked activation of G1 CDKs, followed by retinoblastoma protein phosphorylation. Our results using a PI 3-kinase inhibitor showed that cAMP-dependent PI 3-kinase activation plays an important r...Continue Reading

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Citations

Dec 15, 2010·Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine·Yi Chen, Wen-jian Wang
Jul 12, 2011·Molecular and Cellular Endocrinology·Toshiaki FukushimaShin-Ichiro Takahashi
Apr 17, 2015·Nature Communications·Toshiaki FukushimaShin-Ichiro Takahashi
Jan 28, 2017·Biochemical and Biophysical Research Communications·Toshiaki FukushimaShin-Ichiro Takahashi
Mar 15, 2018·Journal of Molecular Endocrinology·Fumihiko Hakuno, Shin-Ichiro Takahashi
Feb 4, 2012·Molecular Endocrinology·Takeshi AkamaKoichi Suzuki
Jun 22, 2021·Frontiers in Endocrinology·Terry J Smith

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