Fig. 6.

Tyrosine pTyr sites evolved late in SH2 domain proteins. New sites of tyrosine phosphorylation create inter- and intramolecular binding sites for SH2 domains, as illustrated by the proteins Crk, Shc, and Plcγ. (A) The adaptor protein Crk contains an intramolecular tyrosine phosphorylation site that is present in the H. sapiens and D. rerio orthologs but absent in the fruit fly D. melanogaster (DmCrk). Tyrosine phosphorylation at this site by the kinase Abl creates an intramolecular binding site for the Crk SH2 domain. (B) The scaffold Shc contains several Y-x-N (x, any amino acid) motifs that recruit the adaptor protein Grb2. This motif is present in D. melanogaster and all vertebrate paralogs (Shc1-4) but not in the Shc protein from the choanoflagellate M. brevicollis or the nematode C. elegans. (C) SH2 domain proteins within a family can differ in the presence of pTyr sites. Plcγ1 and Plcγ2 contain identical domain organizations, yet only Plcγ1 contains a C terminus pTyr site capable of recruiting SH2 domains. This binding site is present among vertebrates but absent in the choanoflagellate M. brevicollis and fruit fly D. melanogaster. For more examples, see fig. S8.