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SIRPalpha negatively regulates differentiation of PC12 cell
Bin Kang1, Yu Liang, Yunfeng Shan
1International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Brain Research. Molecular Brain Research
|June 21, 2005
Summary
Signal regulatory protein alpha (SIRPalpha) influences neuronal growth and synaptic connections. This study shows SIRPalpha modulates nerve growth factor (NGF)-induced differentiation and cell proliferation by affecting JNK and NF-kappaB pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Signal regulatory protein alpha (SIRPalpha), an Ig superfamily protein, contains an immunoreceptor tyrosine-based inhibitory motif (ITIM).
- SIRPalpha and SHP-2 phosphatase are highly expressed in the brain.
- SIRPalpha promotes neurite outgrowth and is found at synaptogenesis sites.
Purpose of the Study:
- To investigate the role of SIRPalpha in nerve growth factor (NGF)-induced PC12 cell differentiation and proliferation.
- To explore the molecular mechanisms underlying SIRPalpha's neuronal function.
Main Methods:
- Studied SIRPalpha expression during NGF-induced PC12 differentiation.
- Assessed the impact of ectopic SIRPalpha expression on NGF-induced differentiation and proliferation.
- Measured c-jun N-terminal kinase (JNK) and nuclear factor-kappaB (NF-kappaB) activity in SIRPalpha-expressing cells.
Main Results:
- NGF stimulation increased SIRPalpha expression in differentiating PC12 cells.
- Ectopic SIRPalpha expression inhibited NGF-induced morphological differentiation but enhanced proliferation.
- SIRPalpha expression decreased JNK activity and increased NF-kappaB activity.
Conclusions:
- SIRPalpha may stabilize synaptic connections by regulating neurite outgrowth.
- SIRPalpha's neuronal functions are partly mediated through modulation of JNK and NF-kappaB signaling pathways.