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Hyeon Soo Kim  (Kim HS) 2 Articles
Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions
Jie Sha, Jungsik Na, Jung Ok Lee, Nami Kim, Soo Kyung Lee, Ji Hae Kim, Ji Wook Moon, Su Jin Kim, Hye Jeong Lee, Jong-Il Choi, Sun Hwa Park, Hyeon Soo Kim
Endocrinol Metab. 2014;29(3):363-370.   Published online September 25, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.3.363
  • 2,806 View
  • 34 Download
  • 5 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The role of small GTPase molecules is poorly understood under high glucose conditions.

Methods

We analyzed the expression pattern of Vav3 in skeletal muscle C2C12 cells under high glucose culture condition with reverse transcription-polymerase chain reaction and Western blot analysis. We also measured glucose uptake using isotope-labelled glucose.

Results

We showed that expression of Vav3 (a guanine nucleotide exchange factor for RhoA) increased. mRNA and protein levels in skeletal muscle C2C12 cells under high glucose conditions. The AMP-activated protein kinase (AMPK) activator AMPK agonist 5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside (AICAR) suppressed high glucose-induced Vav3 induction. In addition, exposure of cells to high glucose concentration increased the phosphorylation of PAK-1, a molecule downstream of RhoA. The phosphorylation of paxillin, a downstream molecule of PAK-1, was also increased by exposure to high glucose. Phosphorylation of these molecules was not observed in the presence of AICAR, indicating that AMPK is involved in the RhoA signal pathway under high glucose conditions. Knock down of Vav3 enhances metformin-mediated glucose uptake. Inhibition of AMPK blocked the increases of Vav3 knock down-induced glucose uptake. Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.

Conclusion

These results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.

Citations

Citations to this article as recorded by  
  • A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology
    Robert Eckenstaler, Michael Hauke, Ralf A. Benndorf
    Biochemical Pharmacology.2022; 206: 115321.     CrossRef
  • Rho Family GTPases and Rho GEFs in Glucose Homeostasis
    Polly A. Machin, Elpida Tsonou, David C. Hornigold, Heidi C. E. Welch
    Cells.2021; 10(4): 915.     CrossRef
  • Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases
    William Guiler, Addison Koehler, Christi Boykin, Qun Lu
    Frontiers in Cellular Neuroscience.2021;[Epub]     CrossRef
  • Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors
    Nuria Perretta-Tejedor, Javier Fernández-Mateos, Luis García-Ortiz, Manuel A. Gómez-Marcos, José I. Recio-Rodríguez, Cristina Agudo-Conde, Emiliano Rodriguez-Sánchez, Ana I. Morales, Francisco J. López-Hernández, José M. López-Novoa, Rogelio González-Sarm
    Scientific Reports.2017;[Epub]     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
Insulin Phosphorylates Tyrosine Residue 464 of Tub and Translocates Tubby into the Nucleus in HIRcB Cells
Jin Wook Kim, Hyeon Soo Kim, Sang Dae Kim, Jung Yul Park
Endocrinol Metab. 2014;29(2):163-168.   Published online June 26, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.2.163
  • 2,567 View
  • 23 Download
  • 6 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The tubby protein has a motif that might be relevant for its action in the insulin signaling pathway. Previous studies have indicated that tubby undergoes phosphorylation on tyrosine residues in response to several stimuli and is known to localize in the nucleus as well as in the plasma membrane. However, the relationship between phosphorylation and nuclear translocation is not well understood. Here, we report that insulin directly phosphorylates tubby, which translocates into the nucleus.

Methods

The effects of insulin on Tubby were performed with Western blot. The immunoprecipitation and confocal microscopy were performed to prove phosphorylation and nuclear translocation.

Results

Mutation study reveals that tyrosine residue 464 of tubby gene (Tub) is a phosphorylation site activated by insulin. In addition, major portions of tubby protein in the plasma membrane are translocated into the nucleus after insulin treatment. Tyrosine kinase inhibitor pretreatment blocked insulin-induced tubby translocation, suggesting that phosphorylation is important for nuclear translocation. Moreover, mutant tyrosine residue 464 did not translocate into the nucleus in respond to insulin. These findings demonstrate that insulin phosphorylates tyrosine residue 464 of Tub, and this event is important for insulin-induced tubby nuclear translocation.

Conclusion

Insulin phosphorylates tyrosine residue 464 of Tub and translocates tubby into the nuclei of HIRcB cells.

Citations

Citations to this article as recorded by  
  • Shuttling of cellular proteins between the plasma membrane and nucleus (Review)
    Hua-Chuan Zheng, Hua-Mao Jiang
    Molecular Medicine Reports.2021;[Epub]     CrossRef
  • Tubby-like Protein 2 regulates homogalacturonan biosynthesis in Arabidopsis seed coat mucilage
    Meng Wang, Zongchang Xu, Rana Imtiaz Ahmed, Yiping Wang, Ruibo Hu, Gongke Zhou, Yingzhen Kong
    Plant Molecular Biology.2019; 99(4-5): 421.     CrossRef
  • The Caenorhabditis elegans Tubby homolog dynamically modulates olfactory cilia membrane morphogenesis and phospholipid composition
    Danielle DiTirro, Alison Philbrook, Kendrick Rubino, Piali Sengupta
    eLife.2019;[Epub]     CrossRef
  • The tubby-like proteins kingdom in animals and plants
    Meng Wang, Zongchang Xu, Yingzhen Kong
    Gene.2018; 642: 16.     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
  • The Role of Foxo3 in Leydig Cells
    Young Suk Choi, Joo Eun Song, Byung Soo Kong, Jae Won Hong, Silvia Novelli, Eun Jig Lee
    Yonsei Medical Journal.2015; 56(6): 1590.     CrossRef

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