Shin Ichi Hisanaga


Affiliation: Tokyo Metropolitan University
Country: Japan


  1. Takahashi M, Kobayashi Y, Ando K, Saito Y, Hisanaga S. Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT1A receptor via phosphorylation. Biochem Biophys Res Commun. 2019;510:370-375 pubmed publisher
    ..These results suggest that Cdk5-p35 modulates 5-HT signaling through phosphorylation-dependent degradation of 5-HTlAR. ..
  2. Takahashi M, Ishida M, Saito T, Ohshima T, Hisanaga S. Valproic acid downregulates Cdk5 activity via the transcription of the p35 mRNA. Biochem Biophys Res Commun. 2014;447:678-82 pubmed publisher
    ..The chronic administration of VPA also downregulated p35 in mouse brains. These results indicate that VPA regulates Cdk5 activity in neurons via p35 transcription mediated by HDAC inhibition. ..
  3. Sharma G, Tsutsumi K, Saito T, Asada A, Ando K, Tomomura M, et al. Kinase activity of endosomal kinase LMTK1A regulates its cellular localization and interactions with cytoskeletons. Genes Cells. 2016;21:1080-1094 pubmed publisher
    ..Taken together, these results suggest that the kinase activity of LMTK1A regulates the pathway for endosomal vesicles to transfer from microtubules to actin filaments at the tip of growing neurites. ..
  4. Takasugi T, Minegishi S, Asada A, Saito T, Kawahara H, Hisanaga S. Two Degradation Pathways of the p35 Cdk5 (Cyclin-dependent Kinase) Activation Subunit, Dependent and Independent of Ubiquitination. J Biol Chem. 2016;291:4649-57 pubmed publisher
    ..The rapid degradation of p35 by two different methods would be a mechanism to suppress the production of p25, which overactivates Cdk5 to induce neuronal cell death. ..
  5. Kimura T, Hatsuta H, Masuda Suzukake M, Hosokawa M, Ishiguro K, Akiyama H, et al. The Abundance of Nonphosphorylated Tau in Mouse and Human Tauopathy Brains Revealed by the Use of Phos-Tag Method. Am J Pathol. 2016;186:398-409 pubmed publisher
    ..These results indicate that tau molecules are present in multiple phosphorylation states in vivo, and nonphosphorylated forms are highly expressed among them. ..
  6. Hisanaga S, Endo R. Regulation and role of cyclin-dependent kinase activity in neuronal survival and death. J Neurochem. 2010;115:1309-21 pubmed publisher
    ..Appropriate activity, localization, and regulation of Cdk5 may be critical for long-term survival of neurons, which is more than 80 years in the case of humans. ..
  7. Asada A, Yamazaki R, Kino Y, Saito T, Kimura T, Miyake M, et al. Cyclin-dependent kinase 5 phosphorylates and induces the degradation of ataxin-2. Neurosci Lett. 2014;563:112-7 pubmed publisher
    ..These results suggest that Cdk5 controls the abundance of both normal and polyQ-expanded ataxin-2 protein in neurons, which implies that Cdk5 activity is a therapeutic approach for SCA2. ..
  8. Kobayashi H, Saito T, Sato K, Furusawa K, Hosokawa T, Tsutsumi K, et al. Phosphorylation of cyclin-dependent kinase 5 (Cdk5) at Tyr-15 is inhibited by Cdk5 activators and does not contribute to the activation of Cdk5. J Biol Chem. 2014;289:19627-36 pubmed publisher
    ..These results call for reinvestigation of how Cdk5 is regulated downstream of Src family kinases or receptor tyrosine kinases in neurons, which is an important signaling cascade in a variety of neuronal activities. ..
  9. Ito Y, Asada A, Kobayashi H, Takano T, Sharma G, Saito T, et al. Preferential targeting of p39-activated Cdk5 to Rac1-induced lamellipodia. Mol Cell Neurosci. 2014;61:34-45 pubmed publisher
    ..Additionally, we found that p39-Cdk5, but not p35-Cdk5 suppressed lamellipodia formation by reducing Rac1 activity. These results suggest that p39-Cdk5 has a dominant role in Rac1-dependent lamellipodial activity. ..

More Information


  1. Krishnankutty A, Kimura T, Saito T, Aoyagi K, Asada A, Takahashi S, et al. In vivo regulation of glycogen synthase kinase 3β activity in neurons and brains. Sci Rep. 2017;7:8602 pubmed publisher
    ..These results indicate that the Phos-tag SDS-PAGE method provides a simple and appropriate measurement of active GSK3β in vivo, and the activity is regulated by the mechanism other than phosphorylation on Ser9. ..
  2. Tuerde D, Kimura T, Miyasaka T, Furusawa K, Shimozawa A, Hasegawa M, et al. Isoform-independent and -dependent phosphorylation of microtubule-associated protein tau in mouse brain during postnatal development. J Biol Chem. 2018;293:1781-1793 pubmed publisher
    ..These results show for the first time that the phosphorylation and isoform alteration of tau are regulated differently during mouse development. ..