Figure 1. p85α mutations in human cancer.

(A) Cartoon depicting the p85α somatic mutations. Horizontal bar below mutated residues indicates conserved residues across the p85 family members (R1-R3). Black and orange vertical bars indicate previously identified p85α mutations (Jimenez et al., 1998; Jucker et al., 2002; Parsons et al., 2008; Philp et al., 2001; TCGA, 2008; Wood et al., 2007). Orange bars signify hotspots, with the bar height drawn proportional to number of times the residue/region has been altered. (B) p85α somatic mutations modeled on a recent crystal structure (PDB code 2RD0) of p85α iSH2 domain in complex with p110α (Huang et al., 2007). Blue patches on the surface of p110α represent regions that are <3.5Å from p85α iSH2. (C) The p85α residues, N564 and D560 within hydrogen bonding distance of N345 of p110α (Huang et al., 2008; TCGA, 2008) located in the C2 domain is shown. Models of p110β (yellow) and p110δ (purple) C2 domains superimposed on p110α C2 domain (cyan) illustrates the proximity of conserved residue N344 of p110β and N334 of p110δ (corresponding to N345 of p110α) and p85α iSH2 residues D560 and N564. (D) Mutation map of tumors carrying changes in one or more of the genes studied. Each column corresponds to a tumor sample. Pc = pancreatic cancer. ¹Nature 455, 1061, ²Science 321, p1807, ³Science 318, p1108 and ⁴The EMBO journal 17, p743.