6mif

Publication Abstract from PubMed

Dynamic communication between integrin-containing complexes (focal adhesions, FAs) and actin filaments is critical for regulating cell adhesion. Pseudokinase ILK plays a key role in this process but the underlying mechanism remains highly elusive. Here we show that by recruiting FA adaptors PINCH and Parvin into a heterotrimeric complex (IPP), ILK triggers F-actin filament bundling - a process known to generate force/mechanical signal to promote cytoskeleton reassembly and dynamic cell adhesion. Structural, biochemical, and functional analyses revealed that the F-actin bundling is orchestrated by two previously unrecognized WASP-Homology-2 actin binding motifs within IPP, one from PINCH and the other from Parvin. Strikingly, this process is also sensitized to Mg-ATP bound to the pseudoactive site of ILK and its dysregulation severely impairs stress fibers formation, cell spreading, and migration. These data identify a crucial mechanism for ILK, highlighting its uniqueness as a pseudokinase to transduce non-catalytic signal and regulate cell adhesion.

Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion.,Vaynberg J, Fukuda K, Lu F, Bialkowska K, Chen Y, Plow EF, Qin J Nat Commun. 2018 Oct 26;9(1):4465. doi: 10.1038/s41467-018-06906-7. PMID:30367047^[1]

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