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 language | English |
|---|---|
| Pages (from-to) | 18659-18666 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 274 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - 1999 Jun 25 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Physical and functional interactions between pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway
AU - Mochizuki, Toshihiro
AU - Kitanaka, Chifumi
AU - Noguchi, Kohji
AU - Muramatsu, Tomonari
AU - Asai, Akio
AU - Kuchino, Yoshiyuki
PY - 1999/6/25
Y1 - 1999/6/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033603454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033603454&partnerID=8YFLogxK
U2 - 10.1074/jbc.274.26.18659
DO - 10.1074/jbc.274.26.18659
M3 - Article
C2 - 10373478
AN - SCOPUS:0033603454
VL - 274
SP - 18659
EP - 18666
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 26
ER -