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Publication Abstract from PubMed

ILK (integrin-linked kinase) is a distinct intracellular adaptor essential for integrin-mediated cell-extracellular matrix (ECM) adhesion, cell spreading, and migration. Acting as a major docking platform in focal adhesions (FAs), ILK engages many proteins to dynamically link integrins with cytoskeleton, but the underlying mechanism remains elusive. Here we have characterized the interaction of ILK with kindlin-2, a key regulator for integrin bi-directional signaling. We show that human kindlin-2 binds to human ILK with high affinity. Using systematic mapping approaches, we have identified a major ILK binding site involving a 20-residue (339-358) fragment in kindlin-2. NMR-based analysis reveals a helical conformation of this fragment which utilizes its leucine-rich surface to recognize the ILK pseudokinase domain in a mode that is distinct from another ILK pseudokinase domain binding protein, alpha-parvin. Structure-based mutational experiments further demonstrate that the kindlin-2 binding to ILK is crucial for the kindlin-2 localization to FAs and cell spreading (integrin outside-in signaling) but dispensable for the kindlin-2-mediated integrin activation (integrin inside-out signaling). These data define a specific mode of the kindlin-2/ILK interaction with mechanistic implications as to how it spatiotemporally mediates integrin signaling and cell adhesion.

Molecular basis of kindlin-2 binding to integrin-linked kinase (ILK) pseudokinase for regulating cell adhesion.,Fukuda K, Bledzka K, Yang J, Perera HD, Plow EF, Qin J J Biol Chem. 2014 Aug 25. pii: jbc.M114.596692. PMID:25160619^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.