Adhesion stimulates Scar/WAVE phosphorylation in mammalian cells

The Scar/WAVE complex catalyzes the protrusion of pseudopods and lamellipods, and is therefore a principal regulator of cell migration. However, it is unclear how its activity is regulated, beyond a dependence on Rac. Phosphorylation of the proline-rich region, by kinases such as Erk2, has been suggested as an upstream activator. We have recently reported that phosphorylation is not required for complex activation. Rather, it occurs after Scar/WAVE has been activated, and acts as a modulator. Neither chemoattractant signaling nor Erk2 affects the amount of phosphorylation, though in Dictyostelium it is promoted by cell-substrate adhesion. We now report that cell-substrate adhesion also promotes Scar/WAVE2 phosphorylation in mammalian cells, suggesting that the process is evolutionarily conserved.