RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation

Xie, Xiangyang; Chen, Yu; Xue, Peng; Fan, Yong; Deng, Yongqiang; Gong, Peng; Yang, Fuquan; Xu, Tao

doi:10.1038/cr.2009.68

Cited by 20 publications

(10 citation statements)

References 22 publications

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“…This indicates that Reptin silencing increases the sensitivity of HCC cells to insulin, and conversely that the high level of Reptin found in HCC cells likely participates to insulin resistance, a known promoting factor for HCC development . To our knowledge, the regulation of insulin signalling by Reptin in mammalian cells has been so far addressed only in a single study, performed in murine adipocytes, which showed that Reptin silencing reduced the phosphorylation of the Akt substrate AS160, although Akt phosphorylation itself was not examined . This result is opposite to the findings we report here in several HCC cell lines and might be explained by cell‐specific events.…”

Section: Discussioncontrasting

confidence: 99%

Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6

Raymond

Javary

Breig

et al. 2017

Cell Biochemistry & Function

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Hepatocellular carcinoma (HCC) is the main primary cancer of the liver. Many studies have shown that insulin resistance is a risk factor for HCC. We previously discovered the overexpression and oncogenic role of the Reptin/RUVBL2 ATPase in HCC. Here, we found that Reptin silencing enhanced insulin sensitivity in 2 HCC cell lines, as shown by a large potentiation of insulin-induced AKT phosphorylation on Ser473 and Thr308, and of downstream signalling. Reptin silencing did not affect the tyrosine phosphorylation of the insulin receptor nor of IRS1, but it enhanced the tyrosine phosphorylation of the p85 subunit of PI3K. The expression of the SHP-1/PTPN6 phosphatase, which dephosphorylates p85, was reduced after Reptin depletion. Forced expression of SHP-1 restored a normal AKT phosphorylation after insulin treatment in cells where Reptin was silenced, demonstrating that the downregulation of SHP1 is mechanistically linked to increased Akt phosphorylation. In conclusion, we have uncovered a new function for Reptin in regulating insulin signalling in HCC cells via the regulation of SHP-1 expression. We suggest that the regulation of insulin sensitivity by Reptin contributes to its oncogenic action in the liver.

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Section: Discussioncontrasting

confidence: 99%

Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6

Raymond

Javary

Breig

et al. 2017

Cell Biochemistry & Function

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“…Further studies on RuvBs confirmed their involvement in multiple cellular pathways such as cell cycle progression and RNA polymerase IIdirected transcription [8], DNA damage response, replication fork reversal [9], nonsense-mediated mRNA decay [10], insulin stimulated GLUT4 translocation [11], small nucleolar ribonucleotide protein (snoRNPs) assembly [12], cellular transformation, cancer metastasis, apoptosis, mitosis, and development [13,14]. RuvBs are essential components of several complexes of diverse role and it is expected that their mode of function was very similar in these wide range of complexes [14].…”

mentioning

confidence: 72%

Novel RuvB nuclear ATPase is specific to intraerythrocytic mitosis during schizogony of Plasmodium falciparum

Ahmad

Singh

Afrin

et al. 2012

Molecular and Biochemical Parasitology

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“…This may further support the idea that TBC1D1 could compensate for the loss of TBC1D4 S711 phosphorylation in the TBC1D4-S711A-expressing muscles. 7,18,28,29,42), and it is possible that the "signature" phosphorylation patterns induced by upstream kinases on TBC1D1 and TBC1D4 result in differential binding of these partners and thereby distinct regulation of Rab-GAP activity. Similar Rab specificity is likely due to the high homology between TBC1D1 and TBC1D4, especially in the GAP domain of the proteins (30).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

Treebak

Taylor

Witczak

et al. 2010

American Journal of Physiology-Cell Physiology

112

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TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization. The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation. However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites. Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4. The surrounding amino acid sequence predicted that S711 would be recognized by AMPK. Using a phosphospecific antibody against S711, we found that AICAR and contraction increased S711 phosphorylation in mouse skeletal muscle, and this increase was abolished in muscle-specific AMPKalpha2 kinase-dead transgenic mice. Exercise in human vastus lateralis muscle also increased TBC1D4 S711 phosphorylation. Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro. Interestingly, S711 was also phosphorylated in response to insulin in an Akt2- and rapamycin-independent, but a wortmannin-sensitive, manner, suggesting this site is regulated by one or more additional upstream kinases. Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli. S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.

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RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation

Cited by 20 publications

References 22 publications

Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6

Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6

Novel RuvB nuclear ATPase is specific to intraerythrocytic mitosis during schizogony of Plasmodium falciparum

Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

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