Cells engage with their environment through focal adhesions (FAs), large dynamic complexes that link the cytoskeleton to the extracellular matrix. Integrin-linked kinase (ILK) constitutes a hub for integrin-mediated signalling at FAs and forms a tripartite complex with PINCH and parvin – termed the IPP – which interacts with a number of integrin regulators. However, the exact signalling pathways downstream of IPP are not well understood. Indeed, although the interaction between ILK and kindlins is well documented, the lack of molecular details has hindered insight into its significance. By using a conservation-guided mapping approach, David Calderwood and colleagues (Kadry et al., 2018) now identify a previously unknown binding interface for kindlin-2 that comprises highly conserved residues within the C-lobe of the pseudokinase domain (pKD) of ILK. Mutations in the binding site that do not affect the structural integrity of ILK's pKD disrupt, however, interaction of ILK with kindlin-2 and impair its ability to localise to FAs, as well as to rescue the spreading defects exhibited by ILK-knockdown cells. Furthermore, the authors also show that kindlin-2 mutants that cannot bind to ILK are unable to fully support cell spreading. These data clearly demonstrate that the interaction between kindlin-2 and ILK is important for their localisation to FAs and for normal cell spreading, and future work will be aimed at dissecting the specific signalling downstream of the ILK–kindlin-2 axis.
