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. 2015 Mar 18;23(12):1673–1678. doi: 10.1038/ejhg.2015.52

Figure 3.

Figure 3

Characterization of the MAPK/ERK1/2 pathway. (a) Western blot on the whole cell lysate showing reduction of phosphoERK1/2 in the three IgAN cell lines compared with the constitutive activation in the control cell line. Total ERK1/2 and ACTIN were used as loading control. In the graph is presented the ratio between pERK1/2 and actin in the LCL analyzed. (b) Western blot on the whole cell lysate showing reduction of phosphoERK1/2 in all SPRY2 mutation carriers, II-7, III-26, IV-44 and IV-43 cell lines, compared with the constitutive activation in the control cell line and in IV-46, negative for SPRY2 mutations. GAPDH was used as loading control. In the graph is presented the ratio between pERK1/2 and GAPDH in the LCL analyzed. (c) After 7 days of sorafenib treatment LCL157 showed complete block of pERK1/2, increased production of IgA and inhibition of SPRY2 transcription. (d) Cartoon showing the MAPK/ERK pathway with SPRY2 and sorafenib and the effect of the hypo-phosporylated SPRY2 protein on the pathway. In affected individuals mutant SPRY2 is constantly inhibitory, owing to hypophosphorylation.