FIGURE 9.

SHP2 negative feedback acts upstream of STAT3 and MAPK/CREB signaling. A, schematic representation of SHP2 negative feedback signaling. The dashed lines represent recruitment of Ras by SHP2 through the Grb2-SOS scaffold complex, followed by activation of Ras-Raf-MAPK cascade. N2A cells were transfected with scrambled control siRNA, SHP2 siRNA (B), STAT3 siRNA (C), or both SHP2 and STAT3 siRNAs (D), and neurite outgrowth assays were carried out. E, N2A cells were transfected with SHP2 siRNA and then treated with PD for 4 h followed by neurite outgrowth assays. The bar graphs show mean ± S.E. For each graph, neurite outgrowth quantifications were performed from three independent experiments. Statistical differences were calculated using a one-tailed t test. See supplemental Figs. 8S, 9S, 10S, and 11S for statistical significance comparisons of all conditions. *, significance compared with control (Ctrl) siRNA or DMSO pretreatment within the same ligand treatment; *, p < 0.05; **, p < 0.005; ***, p < 0.0005.