Pim‐1 kinase promotes inactivation of the pro‐apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site
Abstract
Constitutive expression of the Pim‐1 kinase prolongs survival of cytokine‐deprived FDCP1 cells, partly via maintenance of Bcl‐2 expression. Here, we show that Pim‐1 colocalizes and physically interacts with the pro‐apoptotic Bad protein and phosphorylates it in vitro on serine 112, which is a gatekeeper site for its inactivation. Furthermore, wild‐type Pim‐1, but not a kinase‐deficient mutant, enhances phosphorylation of this site in FDCP1 cells and protects cells from the pro‐apoptotic effects of Bad. Our results suggest that phosphorylation of Bad by Pim‐1 is one of several mechanisms via which the Pim‐1 kinase can enhance Bcl‐2 activity and promote cell survival.
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PIM kinases promote cancer cell survival by inhibiting apoptosis and by enhancing metabolism and motility via NOTCH1.
“PIM kinases promote cancer cell survival by inhibiting apoptosis for example through phosphorylation of substrates like BAD, and by enhancing metabolism and motility via NOTCH112–14”
From Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (2024) · cites this paper as [13]
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References 30 · Cited by 325
- Authors
- Aho, T. L. T., Sandholm, J., Peltola, K. J., Mankonen, H. P., Lilly, M., & Koskinen, P. J.
- Affiliations
- Åbo Akademi University (FI)
- Loma Linda University Medical Center (US)
- Corresponding author
- Koskinen, Päivi J
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2004-07
- Volume
- 571
- Issue
- 1-3
- Pages
- 43-49
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2140472738
- Cited by
- 325
- References
- 30
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 9 · 2023: 5 · 2022: 9 · 2021: 18 · 2020: 14 · 2019: 10 · 2018: 13 · 2017: 12 · 2016: 17 · 2015: 19 · 2014: 23 · 2013: 23 · 2012: 24
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- PIM-1, BAD protein, Bcl-2, apoptosis, cell survival, protein-protein interaction
- MeSH terms
- Animals, Carrier Proteins, Cell Survival, Chlorocebus aethiops, Glutathione Transferase, Interleukin-3, Kinetics, Phosphorylation, Phosphoserine, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transfection, Apoptosis, Protein Serine-Threonine Kinases, COS Cells, bcl-Associated Death Protein, Proto-Oncogene Proteins c-pim-1
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