Neuroblastoma Tyrosine Kinase Signaling Networks Involve FYN and LYN in Endosomes and Lipid Rafts
Fig 8
Phosphorylation site clusters displayed as a co-clustered correlation networks (CCCNs).
RTK, SFK and PAG1 phosphorylation sites were selected from the co-cluster correlation network shown in S11 Fig, where edges represent Spearman correlations greater than 0.5 from phosphorylation sites that co-clustered from t-SNE embeddings. Edge line thickness is proportional to correlation and the number of cases in which phosphorylation sites co-clustered from different embeddings. Two separate groups containing the most highly phosphorylated RTK and SFK sites are shown. Heat maps (right) show the primary data for phosphorylation on specific sites. (A) The network containing phosphorylation sites ALK 1507 (the most highly phosphorylated site on ALK), FYN 420, PDGFRA 762 and LYN 508 was extended to include other PNCP phosphorylation sites that co-clustered with positive Spearman correlation; no PAG1 phosphorylation sites co-clustered with this group. (B) Five highly phosphorylated PAG1 sites co-clustered with phosphorylation sites on IGF1R, DDR2, EGFR, and FGFR1. Note that the conserved peptide sequence for FYN 531; SRC 530; YES1 537 was inclusively summed to both FYN 531; YES1 537 and SRC 530 in the phosphorylation site network, but exclusively summed to FYN_i in the total protein phosphorylation networks based on the presence of other FYN phosphopeptides in the same samples. By the exclusive criteria, FYN 420; LCK 394; SRC 419; YES1 426 in (A) most likely represents FYN activation; FYN 531; YES1 537 most likely represents FYN inhibitory phosphorylation; and the inclusive summing method likely over-represents the amounts of SRC inhibitory phosphorylation in (B).