Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion

Recent studies suggest that focal adhesion kinase (FAK) is important for ce ll migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell a dhesion and migration. In particular, we observe that FAK is capable of act ivating Stat1, but not Stat3, Co-immunoprecipitation and in vitro binding a ssays demonstrate that Stat1 is transiently and directly associated with FA K during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAK Delta IC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 a ctivation during cell adhesion is diminished in FAK-deficient cells, correl ating with decreased migration in these cells. Finally, we show that deplet ion of Stat1 results in an enhancement of cell adhesion and a decrease in c ell migration. Thus, our results have demonstrated, for the first time, a c ritical signaling pathway from integrin/FAK to Stat1 that reduces cell adhe sion and promotes cell migration,