Chemokines bind to their G protein-coupled receptors (GPCRs) on leukocytes, triggering a series of intracellular signals, which lead to the activation of Rap1 (repressor activator protein 1). Rap1 is crucial for integrin activation. In order to assure anchorage to the cytoskeleton and optimal integrin activation, talin and kindlin 3 must bind to the beta subunit of the integrin. Activated integrins have a fully extended, high-affinity structure, with an open ligand binding site.
GPCR: G protein-coupled receptors; Rac1/RhoA: Ras-related C3 botulinum toxin substrate 1/Ras homolog gene family, member A; CalDAG GEFs: diacylglycerol guanine nucleotide exchange factors; Rap1: repressor activator protein 1; RapL: repressor activator protein lysine.
