Computational data for: Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor

Mitogen-inducible gene 6 (Mig6) is a cellular inhibitor of epidermal
growth factor receptor (EGFR) that binds directly to the EGFR kinase
domain and interferes with signaling. Reduced Mig6 expression is
correlated with increased EGFR activity in multiple cancer models. Here,
we investigated whether disease-associated point mutations could reduce
the inhibitory potency of Mig6. We show that several cancer-associated
mutations, and a mutation derived from Alzheimer's Disease patients,
diminish the ability of Mig6 to bind and inhibit EGFR in vitro. In
mammalian cells, the mutations decreased the Mig6-induced suppression of
basal and EGF-stimulated autophosphorylation, MAP kinase phosphorylation,
and cell migration. To probe the mechanisms by which the mutations could
lead to reduced Mig6 inhibition, we constructed atomic-level computational
models of Mig6 complexed with the EGFR catalytic domain and performed
molecular dynamics simulations for wild-type and mutant complexes.