PMID- 10373478
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase.
      Implications for the Pim-1-mediated activation of the c-Myc signaling pathway.
PG  - 18659-66
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.
FAU - Mochizuki, T
AU  - Mochizuki T
AD  - Biophysics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji,
      Chuo-ku, Tokyo 104-0045, Japan.
FAU - Kitanaka, C
AU  - Kitanaka C
FAU - Noguchi, K
AU  - Noguchi K
FAU - Muramatsu, T
AU  - Muramatsu T
FAU - Asai, A
AU  - Asai A
FAU - Kuchino, Y
AU  - Kuchino Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.7.11.1 (Pim1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
RN  - EC 3.1.3.48 (Cdc25a protein, rat)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (cdc25 Phosphatases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - COS Cells
MH  - Drug Synergism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-myc/*metabolism
MH  - Proto-Oncogene Proteins c-pim-1
MH  - Rats
MH  - *Signal Transduction
MH  - *cdc25 Phosphatases
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18659 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18659-66. doi: 10.1074/jbc.274.26.18659.