Physical and functional interactions between pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway

Toshihiro Mochizuki, Chifumi Kitanaka, Kohji Noguchi, Tomonari Muramatsu, Akio Asai, Yoshiyuki Kuchino

研究成果: Article査読

205 被引用数 (Scopus)

抄録

The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis, but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule(s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A. We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and that also ties Pim-1- mediated mitogenic signals to cell cycle machinery.

本文言語English
ページ(範囲)18659-18666
ページ数8
ジャーナルJournal of Biological Chemistry
274
26
DOI
出版ステータスPublished - 1999 6月 25

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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