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Endocrinol Metab (Seoul). 2014 Jun;29(2):163-8. doi: 10.3803/EnM.2014.29.2.163. Epub 2014 Jun 26.

Insulin Phosphorylates Tyrosine Residue 464 of Tub and Translocates Tubby into the Nucleus in HIRcB Cells.

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Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea.
Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
Department of Neurosurgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
Department of Neurosurgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.



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.


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


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.


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


Insulin; Phosphorylation; Translocation; Tubby

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