How focal adhesion kinase achieves regulation by linking ligand binding, localization and action

Focal adhesion kinase (FAK) has an astonishing number of ligands and functions, which enable it to contribute to embryonic development and human health. FAK can promote different effects in similar cellular environments or similar effects in different cellular environments. Recent advances in structural and cellular analysis of FAK are starting to reveal the interrelationships between the conformations, localizations, interactions, and functions of FAK. This review focuses on our emerging understanding of how the structural framework of FAK mechanistically allows it to integrate manifold stimuli into environment-specific functions.

► Intramolecular and intermolecular interactions of FAK enable environment-specific functions.
► FAK is a scaffolding protein, with a phosphorylation switch between actions.
► Localization controls FAK enrichment, which controls FAK-dependent phosphorylation.
► Serine or tyrosine phosphorylations on FAK trigger different functions.