Figure 3. kiCCA quantifies kinome interactome changes caused by cancer cell plasticity and acute signaling events.

(A) Differential expression analysis (DEA) of kiCCA data revealed that the neuroblastoma lines SK-N-SH and SH-SY5Y have kinome profiles indicative of mesenchymal-noradrenergic plasticity (NMP, Student’s t-test, Benjamini-Hochberg (BH)-FDR < 0.05, n = 22). Kinases marking the noradrenergic and mesenchymal phenotype are highlighted.

(B) Kinases with altered PPI abundance between the SK-N-SH and SH-SY5Y neuroblastoma lines (n = 44 kinase groups, DEA statistics see (A)). Circle size scales with the number of kinase-binding partners that change in abundance.

(C) DEA of high confidence kiCCA interactions reveals that 20 members of a CK2 interaction network showed an altered abundance between neuroblastoma lines (statistics see (A)). Pathway enrichment analysis with STRING 11.5³⁸ showed that differentially abundant CK2 interactors in either cell line participated in distinct signaling pathways.

(D) Co-IP/MS experiments in the SK-N-SH and SH-SY5Y neuroblastoma lines using specific CK2α/β antibodies confirmed altered abundance of CK2 interaction partners as determined by kiCCA.

(E) Overview of kiCCA of EGF-stimulated HeLa cells and annotated kinases with altered PPI abundance upon EGF treatment (n = 63 kinase groups, for DEA statistics see (A)). Kinases with co-regulated changes in phosphorylation and PPIs are highlighted in red. Kinases marked with an asterisk (*) have PPI changes only detected with protein crosslinking.

(F) kiCCA of EGF-stimulated HeLa cells revealed that abundance changes of PPIs correlated with changes in kinase functional states, connecting the EGFR to several non-canonical EGFR-signaling pathways. Network models were created using STRING 11.5.³⁸

See also Figure S4.