Fig. 3.

PKC412 inhibits ZNF198-FGFR1 variants in vitro. (A) Dose-response analysis of Ba/F3 cells stably expressing 4ZF, 10ZF, or PR/TK constructs to PKC412 (Left). Mutation N544D in 4ZF or 10ZF confers drug resistance to PKC412 (Right). The relative viability was normalized to the viability of cells in the absence of PKC412. (B) PKC412 inhibits autophosphorylation of ZNF198-FGFR1. Tyrosine-phosphorylated FGFR1 was assessed by using antiphosphotyrosine antibody 4G10, whereas control ZNF198-FGFR1 protein was probed by a FGFR1 antibody. (C and D) PKC412 abrogates ZNF198-FGFR1-dependent phosphorylation of downstream signaling components PLC-γ and PI3K.