Figure 5

Canonical signaling pathways mediated by KLF11 and mutants. Using the Ingenuity Global Canonical Pathways algorithm, significantly modulated signaling pathways were identified for wild type KLF11 and its mutants. A p-value of less than 0.05 as determined by Fisher’s Exact Test was used as criteria for significant association of focus genes to predetermined pathways curated from published literature. (A) Venn diagram of significant canonical pathways regulated by wild type KLF11 and mutants reveals that the effects of the EAPP mutation are less significant in this experiment compared to the A347S and 486 mutants. These data are supported by the clustering of all significantly regulated targets as shown in (B) which demonstrated that the A347S and Δ486 mutants cluster closely with wild type KLF11 while the EAPP mutant clusters with the empty vector control, indicating complete reversal of the effects of the other proteins. (C) Among the 28 top scoring unique canonical pathways mediated by the 374 mutant are signaling pathways, including, EGF, PDGR, p53, RANK and reelin signaling, and glucocorticoid receptor signaling. The Δ486 (D) and EAPP (E) mutants mediate 4 and 6 pathways respectively, both of which are centered on processes involved on the degradation of biogenic amines. These data support KLF11 as a master transcriptional regulator that mediates large, interconnected signaling cascades.