Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways

Hiraku Ono, Hideyuki Sakoda, Midori Fujishiro, Motonobu Anai, Akifumi Kushiyama, Yasushi Fukushima, Hideki Katagiri, Takehide Ogihara, Yoshitomo Oka, Hideaki Kamata, Nanao Horike, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Carboxy-terminal modulator protein (CTMP) was identified as binding to the carboxy terminus of Akt and inhibiting the phosphorylation and activation of Akt. In contrast to a previous study, we found CTMP overexpression to significantly enhance Akt phosphorylation at both Thr308 and Ser 473 as well as the kinase activity of Akt, while phosphatidylinositol 3-kinase (PI3-kinase) activity was unaffected. Translocation of Akt to the membrane fraction was also markedly increased in response to overexpression of CTMP, with no change in the whole cellular content of Akt. Furthermore, the phosphorylations of GSK-3β and Foxo1, well-known substrates of Akt, were increased by CTMP overexpression. On the other hand, suppression of CTMP with small interfering RNA partially but significantly attenuated this Akt phosphorylation. The cellular activities reportedly mediated by Akt activation were also enhanced by CTMP overexpression. UV-B-induced apoptosis of HeLa cells was significantly reversed not only by over-expression of the active mutant of Akt (myr-Akt) but also by that of CTMP. Increases in glucose transport activity and glycogen synthesis were also induced by overexpression of either myr-Akt or CTMP in 3T3-L1 adipocytes. Taking these results into consideration, it can be concluded that CTMP induces translocation of Akt to the membrane and thereby increases the level of Akt phosphorylation. As a result, CTMP enhances various cellular activities that are principally mediated by the PI3-kinase/Akt pathway.

Original languageEnglish
Pages (from-to)C1576-C1585
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number5
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

Keywords

  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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