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

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)18659-18666
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number26
DOIs
Publication statusPublished - 1999 Jun 25
Externally publishedYes

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Proto-Oncogene Proteins c-pim-1
cdc25 Phosphatases
Phosphoric Monoester Hydrolases
Chemical activation
Cells
Apoptosis
Phosphorylation
Molecules
Protein-Serine-Threonine Kinases
Cell Cycle
Machinery
Phosphotransferases
Cytokines
Oncogenes
Carcinogenesis
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Physical and functional interactions between pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway. / Mochizuki, Toshihiro; Kitanaka, Chifumi; Noguchi, Kohji; Muramatsu, Tomonari; Asai, Akio; Kuchino, Yoshiyuki.

In: Journal of Biological Chemistry, Vol. 274, No. 26, 25.06.1999, p. 18659-18666.

Research output: Contribution to journalArticle

Mochizuki, Toshihiro ; Kitanaka, Chifumi ; Noguchi, Kohji ; Muramatsu, Tomonari ; Asai, Akio ; Kuchino, Yoshiyuki. / Physical and functional interactions between pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 26. pp. 18659-18666.
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