Fig. 4.

CausalPath analysis of Erk2 targets in response to FR. CausalPath subgraphs for Erk2 kinase (MAPK1) responses to FR in both MP41 and MP46 cell lines at FDR ≤ 0.001. Phosphorylation sites are red if increased with FR and blue if decreased. Color intensities for phosphorylation are based on adjusted p-values, as determined by CausalPath. Sites outlined in green are activation by phosphorylation, and those outlined in red are inhibited by phosphorylation. Protein levels are color coded based on log2 fold change with FR (red: increased; blue: decreased). Kinases outlined in red were inactivated by FR. Black boxes indicate coregulated targets of phosphorylation as defined by CausalPath for each cell line. Dashed box indicates targets of phosphorylation that are regulated in common between both cell lines. Several Erk targets, including PRRC2A, NUP153, MED1, GAB1, MBP, and TPR, showed differential patterns of overall phosphorylation between the two cell lines. Most of these differentially phosphorylated sites were linked to other kinases, whereas sites known to be associated with Erk2 showed significant dephosphorylation in both lines. FDR, false discovery rate; MBP, myelin basic protein.