The dynamic remodelling of the actin cytoskeleton is crucial for cell adhesion and motility, and can be triggered by stimuli that activate the insulin receptor (IR) and other receptor tyrosine kinases. IR activation promotes cell motility by disrupting cell-substrate contacts, but many of the steps in this signalling cascade are unknown. On page 2177, Volker Gerke and colleagues now identify a key stage in the pathway – the tyrosine phosphorylation of the phospholipid- and actin-binding protein annexin A2. The authors use baby hamster kidney cells that overexpress the human insulin receptor to show that annexin A2 is tyrosine phosphorylated in response to insulin; in addition, annexin A2 and the IR co-immunoprecipitate, which suggests that the IR phosphorylates annexin A2 directly. Rho/ROCK signalling, the authors show, mediates insulin-induced morphological changes, and knocking down annexin A2 inhibits insulin-triggered Rho activation and actin rearrangements. Importantly, a phosphotyrosine-mimicking annexin A2 mutant induces actin rearrangements in the absence of insulin. The authors propose, therefore, that the tyrosine phosphorylation of annexin A2 links IR activation to Rho/ROCK-mediated actin rearrangement and cell adhesion.