Rodney A Stewart, Takaomi Sanda, Hans R Widlund, Shizhen Zhu, Kenneth D Swanson, Aeron D Hurley, Mohamed Bentires-Alj, David E Fisher, Maria I Kontaridis, A Thomas Look, Benjamin G Neel
The tyrosine phosphatase SHP2 (PTPN11) regulates cellular proliferation, survival, migration, and differentiation during development. Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, which have overlapping clinical features. Paradoxically, Noonan syndrome mutations increase SHP2 phosphatase activity, while LEOPARD syndrome mutants are catalytically impaired, raising the possibility that SHP2 has phosphatase-independent roles. By comparing shp2-deficient zebrafish embryos with those injected with mRNA encoding LEOPARD syndrome point mutations, we identify a phosphatase- and Erk-dependent role for Shp2 in neural crest specification and migration...
May 18, 2010: Developmental Cell