Mutations in the Src homology 2 (SH2)-containing protein-tyrosine phosphatase Shp2
(PTPN11) underlie half of the cases of the autosomal dominant genetic disorder Noonan
syndrome, and somatic Shp2 mutations are found in several hematologic and solid
malignancies. Earlier studies of small numbers of mutants suggested that disease-
associated mutations cause constitutive (SH2 binding-independent) activation and that
cancer-associated mutants are more active than those associated with Noonan syndrome …