SIRPalpha negatively regulates differentiation of PC12 cell.
Signal regulatory protein alpha (SIRPalpha) is an Ig superfamily protein whose cytoplasmic region contains immunoreceptor tyrosine-based inhibitory motif (ITIM), which when tyrosine phosphorylated binds the SH2-domain containing phosphatase 2 (SHP-2). Both SIRPalpha and SHP-2 are highly expressed in brain. Murine cerebellar cells cultured on SIRPalpha-coated surface exhibit enhanced neurite outgrowth and SIRPalpha is localized at sites of synaptogenesis in postnatal mouse brain. In this study, we show that nerve growth factor (NGF) stimulation resulted in elevated SIRPalpha expression during PC12 differentiation. We also show that NGF-induced morphological differentiation, but not growth arrest response, was inhibited by ectopic SIRPalpha expression. PC12 cells stably expressing SIRPalpha proliferated more rapidly than mock-transfected cells. The activity of c-jun N-terminal kinase (JNK) decreased in SIRPalpha-transfected PC12 cells, whereas nuclear factor-kappaB (NF-kappaB) activity increased. Collectively, our results suggest that SIRPalpha may stabilize synaptic connections by inhibiting improper neurite outgrowth and might realize its neuronal function, at least in part, by modulating JNK and NF-kappaB activity.
Kang
Bin
B
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Liang
Yu
Y
Shan
Yunfeng
Y
Guo
Minggao
M
Liu
Shuqin
S
Fu
Xiaoyong
X
Cao
Huifang
H
Wu
Mengchao
M
Wang
Hongyang
H
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006131:Growth Inhibitors / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000943:Antigens, Differentiation; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011971:Receptors, Immunologic; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases