Upon integrin engagement with the extracellular matrix, the Rho GTPases Cdc42 and Rac promote cell spreading and lamellipodium formation. The serine/threonine kinase PAK1, an effector of Cdc42 and Rac, has been implicated in the regulation of cell spreading – but which of the many potential targets of PAK1 is involved in this process? To address this question, Anne Ridley and colleagues (p. 3729) compare wild-type mouse macrophages with those derived from PAK1-null mice (which exhibit immune defects). The authors first show that PAK1–/– macrophages have enhanced cell spreading, but reduced lamellipodial stability. In normal macrophages, the chemoattractant CSF1 transiently stimulates the activation of MAP kinases such as ERK1/2; by contrast, ERK1/2 activation is reduced in CSF1-treated PAK1–/– macrophages, although chemotaxis is unaffected. During adhesion, too, ERK1/2 activity is decreased in the absence of PAK1 – particularly at the cell periphery, where lamellipodia form. Notably, inhibition of ERK1/2 in wild-type macrophages promotes lamellipodial instability and cell spreading. Thus, the authors conclude that PAK1 regulates lamellipodial dynamics through the activation of ERK1/2. Their results shed light on the Rho GTPase-dependent pathways that control cell motility and adhesion.