Journal article
PBK/TOPK, a Proliferating Neural Progenitor-Specific Mitogen-Activated Protein Kinase Kinase
The Journal of neuroscience, v 25(46), pp 10773-10785
01 Nov 2005
PMID: 16291951
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We performed genomic subtraction coupled to microarray-based gene expression profiling and identified the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem cell cultures. Previous studies have identified PBK/TOPK as a mitogen-activated protein kinase (MAPK) kinase that phosphorylated P38 MAPK but with no known expression or function in the nervous system. First, using a novel, bioinformatics-based approach to assess cross-correlation in large microarray datasets, we generated the hypothesis of a cell-cycle-related role for PBK/TOPK in neural cells. We then demonstrated that both PBK/TOPK and P38 are activated in a cell-cycle-dependant manner in neuronal progenitor cells in vitro, and inhibition of this pathway disrupts progenitor proliferation and self-renewal, a core feature of progenitors. In vivo, PBK/TOPK is expressed in rapidly proliferating cells in the adult subependymal zone (SEZ) and early postnatal cerebellar external granular layer. Using an approach based on transgenically targeted ablation and lineage tracing in mice, we show that PBK/TOPK-positive cells in the SEZ are GFAP negative but arise from GFAP-positive neural stem cells during adult neurogenesis. Furthermore, ablation of the adult stem cell population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ. Together, these studies demonstrate that PBK/TOPK is a marker for transiently amplifying neural progenitors in the SEZ. Additionally, they suggest that PBK/TOPK plays an important role in these progenitors, and further implicates the P38 MAPK pathway in general, as an important regulator of progenitor proliferation and self-renewal.
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Details
- Title
- PBK/TOPK, a Proliferating Neural Progenitor-Specific Mitogen-Activated Protein Kinase Kinase
- Creators
- J Dougherty - University of California, Los AngelesADR GarciaI NakanoM LivingstoneB NorrisR PolakiewiczE WexlerM SofroniewH KornblumD Geschwind
- Publication Details
- The Journal of neuroscience, v 25(46), pp 10773-10785
- Publisher
- Society for Neuroscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000233319100022
- Scopus ID
- 2-s2.0-27944434136
- Other Identifier
- 991020099677504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Neurosciences