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Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion

Author

Listed:
  • Julia Vaynberg

    (Lerner Research Institute, Cleveland Clinic)

  • Koichi Fukuda

    (Lerner Research Institute, Cleveland Clinic)

  • Fan Lu

    (Lerner Research Institute, Cleveland Clinic
    School of Medicine, Case Western Reserve University)

  • 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
    School of Medicine, Case Western Reserve University)

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.

Suggested Citation

  • Julia Vaynberg & Koichi Fukuda & Fan Lu & Katarzyna Bialkowska & Yinghua Chen & Edward F. Plow & Jun Qin, 2018. "Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06906-7
    DOI: 10.1038/s41467-018-06906-7
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