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Physical and Functional Interactions between Pim-1 Kinase and Cdc25A Phosphatase
Open accessAbstract
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.
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Cited by
High-throughput retroviral tagging to identify components of specific signaling pathways in cancer
Mikkers, H., Allen, J., Knipscheer, P., Romeyn, L., Hart, A., Vink, E., & Berns, A. (2002) · Nature Genetics · doi:10.1038/ng950 · Cited by 377
Cdc25: mechanisms of checkpoint inhibition and recovery
Karlsson-Rosenthal, C., & Millar, J. B. A. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.04.002 · Cited by 276
Macdonald, A., Campbell, D. G., Toth, R., McLauchlan, H., Hastie, C. J., & Arthur, J. S. C. (2006) · BMC Cell Biology · doi:10.1186/1471-2121-7-1 · Cited by 246
Schuringa, J. J., Chung, K. Y., Morrone, G., & Moore, M. A. S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041024 · Cited by 140
PIM kinases: From survival factors to regulators of cell motility
Santio, N. M., & Koskinen, P. J. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.10.016 · Cited by 69
Metadata
- Authors
- Mochizuki, T., Kitanaka, C., Noguchi, K., Muramatsu, T., Asai, A., & Kuchino, Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 274
- Issue
- 26
- Pages
- 18659-18666
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1987380844
- Cited by
- 244
- References
- 0
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Mochizuki, T., Kitanaka, C., Noguchi, K., Muramatsu, T., Asai, A., & Kuchino, Y. (1999). Physical and Functional Interactions between Pim-1 Kinase and Cdc25A Phosphatase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.26.18659
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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