A novel role for the Ste20 kinase SLK in adhesion signaling and cell migration.

With over 60 members, the Sterile 20 family of kinases has been implicated in numerous biological processes, including growth, survival, apoptosis and cell migration. Recently, we have shown that, in addition to cell death, the Ste20-like kinase SLK is required for efficient cell migration in fibroblasts. We have observed that SLK is involved in cell motility through its effect on actin reorganization and microtubule-induced focal adhesion turnover. Scratch wounding of confluent monolayers results in SLK activation. The induction of SLK kinase activity requires the scaffold FAK and a MAPK-dependent pathway. However, its recruitment to the leading edge of migrating fibroblasts requires the activity of the Src family kinases. Since SLK is microtubule-associated, it may represent one of the signals delivered to focal contacts that induces adhesions turnover. A speculative model is proposed to illustrate the mechanism of SLK activation and recruitment at the leading edge of migrating cells.