Pull and push: Talin activation for integrin signaling

The inside-out signaling of integrins regulates the ligand-binding affinity of the cell surface receptors in response to changes in the environment for cell survival. The specific binding to the cytoplasmic tail of integrin's β subunit by the intracellular protein talin is the key step of inside-out signaling. A “pull-push” mechanism has been proposed to explain how the PIP2-enriched membrane disrupts the dual auto-inhibition of the N-terminal talin-FERM domain by the C-terminal talin-rod domain such that activated talin-FERM can reach the β-tail for integrin activation.