Bifurcation of cell migratory and proliferative signaling by the adaptor protein Shc

Cytokines and extracellular matrix proteins initiate signaling cascades tha t regulate cell migration and proliferation. Evidence is provided that the adaptor protein Shc can differentially regulate these processes. Specifical ly, under growth factor-limiting conditions, Shc stimulates haptotactic cel l migration without affecting anchorage-dependent proliferation, However, w hen growth factors are present, Shc no longer influences cell migration; ra ther, Shc is crucial for DNA synthesis. Mutational analysis of Shc demonstr ates that, while tyrosine phosphorylation is required for both DNA synthesi s and cell migration, the switch in Shc signaling is associated with differ ential use of Shc's phosphotyrosine interacting domains; the PTB domain reg ulates haptotaxis, while the SH2 domain is selectively required for prolife ration.