Signals transmitted through chemokine receptors on rolling neutrophils activate the GTPase Rap-1, in part through CalDAG-GEFI. GTP-bound Rap-1 acts through effectors to convert integrin αLβ2 to an extended, high-affinity conformation, which mediates neutrophil arrest by binding ICAM-1 on endothelial cells. Artz et al demonstrate that TGF-β1 and the distantly related GDF-15 transmit signals through TGF-β–receptor heterodimers, which activate the GTPase Cdc42. GTP-bound Cdc42 inhibits activation of Rap-1, likely by interfering with CalDAG-GEFI. Cdc42, cell division protein 42; GDP, guanosine diphosphate. Illustration by Tadayuki Yago.