FIGURE 9.

Inhibition of ERK MAP kinase and P38 MAP kinase inhibits TGF-β1-stimulated TGF-β1 de novo protein synthesis. A: HK-2 cells were stimulated with TGF-β1 (1 ng/ml) either alone or in combination with PD98059 (8 μmol/L) or SB203580 (0.8 μmol/L) for 48 hours. B: In parallel experiments, to demonstrate specificity of the kinase inhibitors used, cells were stimulated with TGF-β1 in combination with the JNK MAP kinase inhibitor recombinant L-JNKI1 (JNKi) at a concentration of 10 μmol/L. All experiments were performed in the presence of 40 μCi of ³H-radiolabeled amino acid mixture (1000 μCi/ml; Amersham). Supernatant samples were subsequently collected for TGF-β1 immunoprecipitation and radiolabeled TGF-β1 was detected by autoradiography.