Fig. 5.

Weak sequence specificity of oncogenic kinases and autophosphorylated sites. Using the AROC as a proxy for the degree of sequence specificity, we compared several subsets of kinases and SH2 domains. (A) Serine/threonine (S/T) kinases exhibit stronger sequence specificity (higher AROC) than tyrosine (Y) kinases (P < 10⁻¹⁰). Tyrosine kinases with SH2 domains are less specific (lower AROC) than other tyrosine kinases (P < 10⁻³). (B) Oncogenic tyrosine kinases, as defined by the Cancer Genome Project (56), have lower AROC than their non-oncogenic counterparts (P < 0.003). Error bars show the 90% confidence intervals and statistical significance was tested by Student’s t test. (C) The score distribution of serine/threonine autophosphorylation sites in 10 kinases is shifted toward low values, whereas the random expectation would be a uniform distribution (P < 0.04; see Methods). This shows that autophosphorylation sites typically have weaker sequence motifs than other sites phosphorylated by the same kinase.