CDK5-dependent phosphorylation of the Rho family GTPase TC10α regulates insulin-stimulated GLUT4 translocation

Shuichi Okada, Eijiro Yamada, Tsugumichi Saito, Kihachi Ohshima, Koshi Hashimoto, Masanobu Yamada, Yutaka Uehara, Takafumi Tsuchiya, Hiroyuki Shimizu, Kazuaki Tatei, Takashi Izumi, Keishi Yamauchi, Shin Ichi Hisanaga, Jeffrey E. Pessin, Masatomo Mori

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Insulin stimulation results in the activation of cyclin-dependent kinase-5 (CDK5) in lipid raft domains via a Fyn-dependent phosphorylation on tyrosine residue 15. In turn, activated CDK5 phosphorylates the Rho family GTP-binding protein TC10α on threonine 197 that is sensitive to the CDK5 inhibitor olomoucine and blocked by small interfering RNA-mediated knockdown of CDK5. The phosphorylation deficient mutant T197A-TC10α was not phosphorylated and excluded from the lipid raft domain, whereas the phosphorylation mimetic mutant (T197D-TC10α) was lipid raft localized. Insulin resulted in the GTP loading of T197D-TC10α but not T197A-TC10α and in parallel, T197D-TC10α but not T197A-TC10α depolymerized cortical actin and inhibited insulin-stimulated GLUT4 translocation. These data demonstrate that CDK5-dependent phosphorylation maintains TC10α in lipid raft compartments thereby disrupting cortical actin, whereas subsequent dephosphorylation of TC10α through inactivation of CDK5 allows for the re-assembly of F-actin. Because cortical actin reorganization is required for insulin-stimulated GLUT4 translocation, these data are consistent with a CDK5-dependent TC10α cycling between lipid raft and non-lipid raft compartments.

Original languageEnglish (US)
Pages (from-to)35455-35463
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number51
DOIs
StatePublished - Dec 19 2008

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Cyclin-Dependent Kinase 5
rho GTP-Binding Proteins
Phosphorylation
GTP Phosphohydrolases
Insulin
Actins
Lipids
Threonine
Guanosine Triphosphate
GTP-Binding Proteins
Small Interfering RNA
Tyrosine
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Okada, S., Yamada, E., Saito, T., Ohshima, K., Hashimoto, K., Yamada, M., ... Mori, M. (2008). CDK5-dependent phosphorylation of the Rho family GTPase TC10α regulates insulin-stimulated GLUT4 translocation. Journal of Biological Chemistry, 283(51), 35455-35463. https://doi.org/10.1074/jbc.M806531200

CDK5-dependent phosphorylation of the Rho family GTPase TC10α regulates insulin-stimulated GLUT4 translocation. / Okada, Shuichi; Yamada, Eijiro; Saito, Tsugumichi; Ohshima, Kihachi; Hashimoto, Koshi; Yamada, Masanobu; Uehara, Yutaka; Tsuchiya, Takafumi; Shimizu, Hiroyuki; Tatei, Kazuaki; Izumi, Takashi; Yamauchi, Keishi; Hisanaga, Shin Ichi; Pessin, Jeffrey E.; Mori, Masatomo.

In: Journal of Biological Chemistry, Vol. 283, No. 51, 19.12.2008, p. 35455-35463.

Research output: Contribution to journalArticle

Okada, S, Yamada, E, Saito, T, Ohshima, K, Hashimoto, K, Yamada, M, Uehara, Y, Tsuchiya, T, Shimizu, H, Tatei, K, Izumi, T, Yamauchi, K, Hisanaga, SI, Pessin, JE & Mori, M 2008, 'CDK5-dependent phosphorylation of the Rho family GTPase TC10α regulates insulin-stimulated GLUT4 translocation', Journal of Biological Chemistry, vol. 283, no. 51, pp. 35455-35463. https://doi.org/10.1074/jbc.M806531200
Okada, Shuichi ; Yamada, Eijiro ; Saito, Tsugumichi ; Ohshima, Kihachi ; Hashimoto, Koshi ; Yamada, Masanobu ; Uehara, Yutaka ; Tsuchiya, Takafumi ; Shimizu, Hiroyuki ; Tatei, Kazuaki ; Izumi, Takashi ; Yamauchi, Keishi ; Hisanaga, Shin Ichi ; Pessin, Jeffrey E. ; Mori, Masatomo. / CDK5-dependent phosphorylation of the Rho family GTPase TC10α regulates insulin-stimulated GLUT4 translocation. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 51. pp. 35455-35463.
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AU - Okada, Shuichi

AU - Yamada, Eijiro

AU - Saito, Tsugumichi

AU - Ohshima, Kihachi

AU - Hashimoto, Koshi

AU - Yamada, Masanobu

AU - Uehara, Yutaka

AU - Tsuchiya, Takafumi

AU - Shimizu, Hiroyuki

AU - Tatei, Kazuaki

AU - Izumi, Takashi

AU - Yamauchi, Keishi

AU - Hisanaga, Shin Ichi

AU - Pessin, Jeffrey E.

AU - Mori, Masatomo

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