Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion

Julia Vaynberg, Koichi Fukuda, Fan Lu, Katarzyna Bialkowska, Yinghua Chen, Edward F. Plow and Jun Qin ()
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Julia Vaynberg: Lerner Research Institute, Cleveland Clinic
Koichi Fukuda: Lerner Research Institute, Cleveland Clinic
Fan Lu: Lerner Research Institute, Cleveland Clinic
Katarzyna Bialkowska: Lerner Research Institute, Cleveland Clinic
Yinghua Chen: School of Medicine, Case Western Reserve University
Edward F. Plow: Lerner Research Institute, Cleveland Clinic
Jun Qin: Lerner Research Institute, Cleveland Clinic

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06906-7

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