Fig. 7.

Evolution of pTyr networks. (A) The structures indicate the degree of sequence conservation of the SH2 domains of Grb2 (PDB 1BMB), Crk (PDB 1JU5), and Nck (PDB 2CI9) mapped onto the tertiary structure. The surface representations are colored according to the amount of conservation and the bound pTyr peptide is indicated (gray). The region of the PTB pocket is highlighted with a black box. (B) A regional pTyr interaction network for Grb2, Crk, and Nck (Dock in fruit fly) is shown for the fruit fly D. melanogaster. SH2 interactions for these domains were predicted with mammalian SH2 specificity data. Solid black lines indicate SH2-mediated interactions; dashed lines represent PTB-mediated interactions. A blue line indicates an SH3-dependent interaction. Components of the pTyr network shown as colored circles are SH2 adaptor proteins (yellow), scaffolds (blue), tyrosine kinases (green), or signal regulators (orange). (C) The equivalent mammalian pTyr network for these SH2 adaptor proteins from experimentally validated and tested interactions reveals that additional connections are present in mammals.