Cancer TK circuits preferably make use of multifunctional substrates and highly connected pTyr sites. (A) Cancer TK circuits are highly connected. Shown in the graph is a correlation between the frequency of a pTyr site to be detected from cancer samples (x-axis) and the number of SH2/PTB domains, TKs, or circuits connected to that site, based on the predicted data set. The cancer pTyr sites are divided into five groups (based on frequency of detection) to ensure that each group has at least 10% of the total cancer pTyr sites. (B) TK circuits identified with high frequency in cancer samples are significantly enriched in multifunctional substrates of the primitive (P), bilaterian (B), and vertebrate (V) origin. The substrates corresponding to the high-frequency cancer (HFC) pTyr sites are divided into either the SRS (singular-role substrate) or the DRS (dual-role substrate) group according to the absence or presence of a kinase and/or an SH2/PTB domain in the same substrate. Bar graph: comparison in the number (shown in percentage) of HFC pTyr sites in the SRS and DRS groups. The substrates are classified according to their evolutionary origins. DRSs of the P-, B-, and V-origin are significantly enriched in cancer signaling. P-values were calculated using χ2 test.
