Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization

J Cell Biol. 2008 Feb 25;180(4):681-9. doi: 10.1083/jcb.200710074. Epub 2008 Feb 18.

Abstract

Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry-based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. alpha- and beta-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A-TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Aurora Kinases
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Centrosome / enzymology*
  • Centrosome / ultrastructure
  • Chromosome Segregation / genetics*
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Down-Regulation / genetics
  • HeLa Cells
  • Humans
  • Mass Spectrometry
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / genetics*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary / genetics
  • Spindle Apparatus / enzymology*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / ultrastructure
  • Tubulin / chemistry
  • Tubulin / metabolism

Substances

  • CKAP5 protein, human
  • Carrier Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Tubulin
  • integrin-linked kinase
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human