Serine 785 phosphorylation of the beta1 cytoplasmic domain modulates beta1A-integrin-dependent functions.

The integrin beta1 cytoplasmic domain plays a key role in a variety of integrin-mediated events including adhesion, migration and signaling. A number of studies suggest that phosphorylation may modify the functional state of the cytoplasmic domain, but these studies frequently only examine the effect of substituting amino acid mimics that cannot be phosphorylated. We now demonstrate, using site directed mutagenesis, that substituting either an unphosphorylated (S to M) or a phosphorylated (S to D) mimic in place of serine can modify integrin function. Specifically, we show that expressing a residue that mimics a dephosphorylated form of the protein promotes cell spreading and directed cell migration, whereas a residue mimicking a phosphorylated form of the protein promotes attachment but inhibits cell spreading or migration. The significance of these observations is strengthened by the fact that the beta1 mutations display the same properties in both a fibroblast cell line (GD25) and a teratocarcinoma cell line (F9). The results indicate that changes in the phosphorylation state of S785 modulates beta1 integrin function.