Fig. 1. Signalling pathways that control integrin function. The extracellular domains of inactive integrins are folded and display a conformation that has a low affinity for ligands. The inside-out signalling pathway activates integrins by inducing conformational changes that open the extracellular domains into a high-affinity ligand-binding state. Inside-out signalling is triggered intracellularly in response to external stimuli. Shown are surface receptors that are known to activate β2 integrins. The small GTPase Rap1 is a potent mediator of integrin inside-out signalling and activation. Rap1 is activated downstream of surface receptors. At least two downstream effectors of Rap1 have been shown to be involved in the activation of integrin function: RapL acts on the -subunit of the Lβ2 integrin and RIAM is proposed to stimulate the binding of talin to the membrane-proximal NPX[Y/F] motif of the β-subunits. The binding of talin to the cytoplasmic tail of β-subunits is sufficient for integrin activation and characterises the active state of integrins. The binding of ligand to the extracellular domains of activated integrins stimulates outside-in signalling pathways, i.e. the activation and/or recruitment of multiple structural (e.g. vinculin, paxillin and actin) and signalling (e.g. p130Cas, FAK and Rho GTPases) proteins, leading to the remodelling of the actin cytoskeleton and the formation of adhesion structures.