Abstract
HiB5 is a multipotent hippocampal stem cell line whose differentiation into cells of a neuronal phenotype is promoted by neurotrophic factors such as PDGF and brain-derived neurotrophic factor (BDNF). We examined the potential role of Src homology 2 (SH2)-containing protein tyrosine phosphatase (Shp2) in this differentiation process. We found that Shp2 became tyrosine phosphorylated following PDGF treatment. Wild-type Shp2 enhanced the expression of neurofilament, synapsin I and PSD95 by PDGF and BDNF, whereas their expression was attenuated by the catalytically inactive mutants Shp2C/S and Shp2ΔP. Formation of dendritic spine-like structures increased with wild-type Shp2, but diminished with Shp2C/S and Shp2ΔP. PSD95, localized in the post-synaptic density region of dendritic spines, PDGFRβ and TrkB were co-immunoprecipitated with Shp2 antibodies. These results suggest that Shp2 plays a positive role in mediating PDGF- and BDNF-activated signaling which promotes the formation of dendritic spines.
Original language | English |
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Pages (from-to) | 750-754 |
Number of pages | 5 |
Journal | Archives of Pharmacal Research |
Volume | 30 |
Issue number | 6 |
DOIs | |
Publication status | Published - 30 Jun 2007 |
Bibliographical note
Funding Information:This work was supported by grants from the Brain Research Center (M103KV010007-06K2201-00710) of the 21C Frontier Research program by MOST, the Korea Health 21R&D Project (0405-DB01-0104-0006) by MOHW, and the BK21 by MOE to Y.K.K. and Ministry of Health & Welfare (O0-PJ9-PG1-CO05-0002) to H.K. We also thank the Korea Basic Science Institute for the support of laser scanning microscopy.
Keywords
- BDNF
- Differentiation
- Neuron
- PDGF
- Shp2