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KMID : 0043320070300060750
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Archives of Pharmacal Research
2007 Volume.30 No. 6 p.750 ~ p.754
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Shp2 is Involved in Neuronal Differentiation of Hippocampal Precursor Cells
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Kim Hak-Jae
Han Ah-Mi
Shim Jae-Hwan
Yoon Hye-Hyun
Kwon Hyock-Man
Kim Yun-Hee
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Abstract
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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 Shp2?P. Formation of dendritic spine-like structures increased with wild-type Shp2, but diminished with Shp2C/S and Shp2?P. PSD95, localized in the post-synaptic density region of dendritic spines, PDGFR?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.
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KEYWORD
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Shp2, PDGF, BDNF, Neuron, Differentiation
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