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Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization
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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265580/ https://www.ncbi.nlm.nih.gov/pubmed/18283114 http://dx.doi.org/10.1083/jcb.200710074 |
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author | Fielding, Andrew B. Dobreva, Iveta McDonald, Paul C. Foster, Leonard J. Dedhar, Shoukat |
author_facet | Fielding, Andrew B. Dobreva, Iveta McDonald, Paul C. Foster, Leonard J. Dedhar, Shoukat |
author_sort | Fielding, Andrew B. |
collection | PubMed |
description | 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. α- and β-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. |
format | Text |
id | pubmed-2265580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22655802008-08-25 Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization Fielding, Andrew B. Dobreva, Iveta McDonald, Paul C. Foster, Leonard J. Dedhar, Shoukat J Cell Biol Research Articles 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. α- and β-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. The Rockefeller University Press 2008-02-25 /pmc/articles/PMC2265580/ /pubmed/18283114 http://dx.doi.org/10.1083/jcb.200710074 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Fielding, Andrew B. Dobreva, Iveta McDonald, Paul C. Foster, Leonard J. Dedhar, Shoukat Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title_full | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title_fullStr | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title_full_unstemmed | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title_short | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
title_sort | integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265580/ https://www.ncbi.nlm.nih.gov/pubmed/18283114 http://dx.doi.org/10.1083/jcb.200710074 |
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