Research output: Contribution to Journal/Magazine › Journal article › peer-review
Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization. / Fielding, Andrew B.; Dobreva, Iveta; McDonald, Paul C et al.
In: Journal of Cell Biology, Vol. 180, No. 4, 25.02.2008, p. 681-9.Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization
AU - Fielding, Andrew B.
AU - Dobreva, Iveta
AU - McDonald, Paul C
AU - Foster, Leonard J
AU - Dedhar, Shoukat
PY - 2008/2/25
Y1 - 2008/2/25
N2 - 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.
AB - 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.
KW - ATPases Associated with Diverse Cellular Activities
KW - Aurora Kinases
KW - Carrier Proteins
KW - Centrosome
KW - Chromosome Segregation
KW - DNA Helicases
KW - Down-Regulation
KW - HeLa Cells
KW - Humans
KW - Mass Spectrometry
KW - Microtubule-Associated Proteins
KW - Mitosis
KW - Nuclear Proteins
KW - Protein Structure, Tertiary
KW - Protein-Serine-Threonine Kinases
KW - Spindle Apparatus
KW - Tubulin
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1083/jcb.200710074
DO - 10.1083/jcb.200710074
M3 - Journal article
C2 - 18283114
VL - 180
SP - 681
EP - 689
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 4
ER -