SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration.

Focal adhesion turnover is a complex process required for cell migration. We have previously shown that the Ste20-like kinase (SLK) is required for cell migration and efficient focal adhesion (FA) turnover in a FA kinase (FAK)-dependent manner. However, the role of SLK in this process remains unclear. Using a candidate substrate approach, we show that SLK phosphorylates the adhesion adapter protein paxillin on serine 250. Serine 250 phosphorylation is required for paxillin redistribution and cell motility. Mutation of paxillin serine 250 prevents its phosphorylation by SLK in vitro and results in impaired migration in vivo as evidenced by an accumulation of phospho-FAK-Tyr397 and altered FA turnover rates. Together, our data suggest that SLK phosphorylation of paxillin on serine 250 is required for FAK-dependent FA dynamics.