Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion

Vaynberg, Julia; Fukuda, Koichi; Lu, Fan; Bialkowska, Katarzyna; Chen, Yinghua; Plow, Edward F.; Qin, Jun

doi:10.1038/s41467-018-06906-7

Title: Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion

Journal Article · Fri Oct 26 00:00:00 EDT 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-06906-7· OSTI ID:1483387

Vaynberg, Julia ^[1]; Fukuda, Koichi ^[1]; Lu, Fan ^[2]; Bialkowska, Katarzyna ^[1]; Chen, Yinghua ^[3]; Plow, Edward F. ^[1]; Qin, Jun ^[2]

Cleveland Clinic, Cleveland, OH (United States)
Cleveland Clinic, Cleveland, OH (United States); Case Western Reserve Univ., Cleveland, OH (United States)
Case Western Reserve Univ., Cleveland, OH (United States)

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 in this paper 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.

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Research Organization:: Cleveland Clinic, Cleveland, OH (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357; HL058758; 1S10RR026820-01

OSTI ID:: 1483387

Journal Information:: Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 41 works

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