SHP-2 regulates PC12 cell survival and apoptosis in response to NGF via activation of ERK and JNK

AIM: To investigate the central role of the protein tyrosine phosphatase SHP-2 in the survival of PC12 cells upon NGF treatment and apoptosis after NGF withdrawal. METHODS: PC12 cells were treated with SHP-2 inhibitor (NSC87877). Cell survival rate was detected by MTT method and apoptosis was determined by flow cytometry. Moreover, pIRES-GFP (vector alone), pIRES-GFP-SHP-2 (wild type) and pIRES-GFP-SHP-2C459S (dominant negative mutant form) were transfected into PC12 cells. ERK, p-ERK, JNK and p-JNK were immunoblotted at 1 h in the presence of NGF and 5 h after NGF withdrawal. RESULTS: SHP-2 potentially enhanced survival and attenuated apoptosis of PC12 cells. The activation of ERK was significantly enhanced with NGF treatment either in the group without SHP-2 inhibitor or the SHP-2 wild type group. On the other hand, phosphorylation level of JNK was significantly increased after NGF withdrawal when PC12 cells were treated with SHP-2 inhibitor or transfected with SHP-2 mutant. CONCLUSION: SHP-2 may play a central role in mediating the survival and apoptosis of PC12 cells upon NGF exposure and withdrawal. The underlying mechanisms may be through the activation of ERK and JNK.