IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.
IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.
复制标题
亮氨酸剥夺引起的 IGFBP-1 过度磷酸化是由 AAR 途径介导的。
DOI：
10.1016/j.mce.2015.04.031
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发表时间：
2015-09-05
影响因子：
4.1
通讯作者：
Gupta MB
中科院分区：
文献类型：
--
作者：
Malkani N;Jansson T;Gupta MB
胰岛素样生长因子-1（IGF-I）是胎儿生长的关键调节因子。IGF结合蛋白-1（IGFBP-1）磷酸化显著降低IGF-I的生物利用度。亮氨酸剥夺可诱导IGFBP-1过度磷酸化，在胎儿生长受限（FGR）中起重要作用。FGR的特征在于氨基酸可用性降低，其激活氨基酸反应（AAR）并抑制雷帕霉素（mTOR）通路的机制靶点。我们研究了AAR和mTOR在亮氨酸剥夺的HepG 2细胞中介导IGFBP-1分泌和磷酸化的作用。mTOR抑制（雷帕霉素或raptor+rictor siRNA）或激活（DEPTOR siRNA）证实了mTOR在亮氨酸剥夺诱导的IGFBP-1分泌中的作用，但不是磷酸化。当AAR被阻断（U 0126或ERK/GCN 2 siRNA）时，由于亮氨酸剥夺导致的IGFBP-1分泌和磷酸化（Ser 101/Ser 119/Ser 169）都被阻止。TBB对CK 2的抑制也减弱了亮氨酸剥夺时IGFBP-1的磷酸化。这些结果表明，AAR和mTOR独立调节IGFBP-1分泌和磷酸化亮氨酸剥夺。
Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor+rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and phosphorylation (Ser101/Ser119/Ser169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in leucine deprivation.
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DOI：
10.2741/s162
发表时间：
2011-01-01
期刊：
Frontiers in bioscience (Scholar edition)
影响因子：
--
作者：
Brown LD;Green AS;Limesand SW;Rozance PJ
通讯作者：
Rozance PJ
影响因子：
4.4
作者：
Abu Shehab, Majida;Khosravi, Javad;Gupta, Madhulika B.
通讯作者：
Gupta, Madhulika B.
影响因子：
4.8
作者：
Arsham, AM;Howell, JJ;Simon, MC
通讯作者：
Simon, MC
DOI：
10.1152/ajpendo.91000.2008
发表时间：
2009-12-01
影响因子：
5.1
作者：
Chotechuang, Nattida;Azzout-Marniche, Dalila;Tome, Daniel
通讯作者：
Tome, Daniel
影响因子：
4.8
作者：
Abu Shehab, Majida;Damerill, Ian;Gupta, Madhulika B.
通讯作者：
Gupta, Madhulika B.