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...
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| Veröffentlicht in: | The Journal of cell biology 2008-02, Vol.180 (4), p.681-689 |
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| creator | Fielding, Andrew B Dobreva, Iveta McDonald, Paul C Foster, Leonard J Dedhar, Shoukat |
| 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. |
| doi_str_mv | 10.1083/jcb.200710074 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200710074</identifier><identifier>PMID: 18283114</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Antibodies ; ATPases Associated with Diverse Cellular Activities ; Aurora Kinases ; Carrier Proteins - chemistry ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell division ; Centrosome - enzymology ; Centrosome - ultrastructure ; Centrosomes ; Chromosome Segregation - genetics ; Chromosomes ; Deoxyribonucleic acid ; DNA ; DNA Helicases - chemistry ; DNA Helicases - genetics ; DNA Helicases - metabolism ; Down-Regulation - genetics ; Focal adhesions ; Gene expression ; Gene expression regulation ; HEK293 cells ; HeLa Cells ; Humans ; Kinases ; Mass Spectrometry ; Microtubule-Associated Proteins - chemistry ; Microtubule-Associated Proteins - metabolism ; Microtubules ; Mitosis ; Mitosis - genetics ; Mitotic spindle apparatus ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Protein Structure, Tertiary - genetics ; Protein-Serine-Threonine Kinases - chemistry ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Proteomics ; Small interfering RNA ; Spindle Apparatus - enzymology ; Spindle Apparatus - genetics ; Spindle Apparatus - ultrastructure ; Tubulin - chemistry ; Tubulin - metabolism</subject><ispartof>The Journal of cell biology, 2008-02, Vol.180 (4), p.681-689</ispartof><rights>Copyright 2008 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press Feb 25, 2008</rights><rights>Copyright © 2008, The Rockefeller University Press 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-723eea382da2a0b788e2f57709bc2c7b6efcf7ec912a8186759b9252237a4d953</citedby><cites>FETCH-LOGICAL-c555t-723eea382da2a0b788e2f57709bc2c7b6efcf7ec912a8186759b9252237a4d953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18283114$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fielding, Andrew B</creatorcontrib><creatorcontrib>Dobreva, Iveta</creatorcontrib><creatorcontrib>McDonald, Paul C</creatorcontrib><creatorcontrib>Foster, Leonard J</creatorcontrib><creatorcontrib>Dedhar, Shoukat</creatorcontrib><title>Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><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.</description><subject>Antibodies</subject><subject>ATPases Associated with Diverse Cellular Activities</subject><subject>Aurora Kinases</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell division</subject><subject>Centrosome - enzymology</subject><subject>Centrosome - ultrastructure</subject><subject>Centrosomes</subject><subject>Chromosome Segregation - genetics</subject><subject>Chromosomes</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Helicases - chemistry</subject><subject>DNA Helicases - genetics</subject><subject>DNA Helicases - metabolism</subject><subject>Down-Regulation - genetics</subject><subject>Focal adhesions</subject><subject>Gene expression</subject><subject>Gene expression regulation</subject><subject>HEK293 cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinases</subject><subject>Mass Spectrometry</subject><subject>Microtubule-Associated Proteins - chemistry</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Microtubules</subject><subject>Mitosis</subject><subject>Mitosis - genetics</subject><subject>Mitotic spindle apparatus</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Protein-Serine-Threonine Kinases - chemistry</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Small interfering RNA</subject><subject>Spindle Apparatus - enzymology</subject><subject>Spindle Apparatus - genetics</subject><subject>Spindle Apparatus - ultrastructure</subject><subject>Tubulin - chemistry</subject><subject>Tubulin - metabolism</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEokvhyBGIOHBLGY_j2LkgoYqPSpU4QI_IcpzJ1tusvdgOEv31uOxq-bhwsHx4H41m3qeqnjI4Y6D4640dzhBAsvLae9WKiRYaxVq4X60AkDW9QHFSPUppAwCtbPnD6oQpVJyxdlV9vfCZ1tH5Znb-hsb6xnmTqJ6DNbO7pVTnUOdrqi35HEMKW6qNH-tI62U2ueRbl0N2tk4758eZ6hDXxrtbk13wj6sHk5kTPTn8p9XV-3dfzj82l58-XJy_vWysECI3EjmR4QpHgwYGqRThJKSEfrBo5dDRZCdJtmdoFFOdFP3Qo0Dk0rRjL_hp9WY_d7cMWxp_7WpmvYtua-IPHYzTfyfeXet1-K4ROyEUlAGvDgNi-LZQynrrkqV5Np7CkrQE3rIO5X9BBNHJoqKAL_8BN2GJvrSgkRVbHPnd3s0esqXaFGk6rsxA3-nVRa8-6i388z_v_E0ffBbg2R7YpBziMccivpzZlfzFPp9M0KZ4T_rqMwLjAKo00Qr-E49StLI</recordid><startdate>20080225</startdate><enddate>20080225</enddate><creator>Fielding, Andrew B</creator><creator>Dobreva, Iveta</creator><creator>McDonald, Paul C</creator><creator>Foster, Leonard J</creator><creator>Dedhar, Shoukat</creator><general>The Rockefeller University Press</general><general>Rockefeller University Press</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080225</creationdate><title>Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization</title><author>Fielding, Andrew B ; Dobreva, Iveta ; McDonald, Paul C ; Foster, Leonard J ; Dedhar, Shoukat</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-723eea382da2a0b788e2f57709bc2c7b6efcf7ec912a8186759b9252237a4d953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antibodies</topic><topic>ATPases Associated with Diverse Cellular Activities</topic><topic>Aurora Kinases</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell division</topic><topic>Centrosome - enzymology</topic><topic>Centrosome - ultrastructure</topic><topic>Centrosomes</topic><topic>Chromosome Segregation - genetics</topic><topic>Chromosomes</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Helicases - chemistry</topic><topic>DNA Helicases - genetics</topic><topic>DNA Helicases - metabolism</topic><topic>Down-Regulation - genetics</topic><topic>Focal adhesions</topic><topic>Gene expression</topic><topic>Gene expression regulation</topic><topic>HEK293 cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinases</topic><topic>Mass Spectrometry</topic><topic>Microtubule-Associated Proteins - chemistry</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Microtubules</topic><topic>Mitosis</topic><topic>Mitosis - genetics</topic><topic>Mitotic spindle apparatus</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Protein-Serine-Threonine Kinases - chemistry</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Small interfering RNA</topic><topic>Spindle Apparatus - enzymology</topic><topic>Spindle Apparatus - genetics</topic><topic>Spindle Apparatus - ultrastructure</topic><topic>Tubulin - chemistry</topic><topic>Tubulin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fielding, Andrew B</creatorcontrib><creatorcontrib>Dobreva, Iveta</creatorcontrib><creatorcontrib>McDonald, Paul C</creatorcontrib><creatorcontrib>Foster, Leonard J</creatorcontrib><creatorcontrib>Dedhar, Shoukat</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fielding, Andrew B</au><au>Dobreva, Iveta</au><au>McDonald, Paul C</au><au>Foster, Leonard J</au><au>Dedhar, Shoukat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2008-02-25</date><risdate>2008</risdate><volume>180</volume><issue>4</issue><spage>681</spage><epage>689</epage><pages>681-689</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><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. 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.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>18283114</pmid><doi>10.1083/jcb.200710074</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies ATPases Associated with Diverse Cellular Activities Aurora Kinases Carrier Proteins - chemistry Carrier Proteins - genetics Carrier Proteins - metabolism Cell division Centrosome - enzymology Centrosome - ultrastructure Centrosomes Chromosome Segregation - genetics Chromosomes Deoxyribonucleic acid DNA DNA Helicases - chemistry DNA Helicases - genetics DNA Helicases - metabolism Down-Regulation - genetics Focal adhesions Gene expression Gene expression regulation HEK293 cells HeLa Cells Humans Kinases Mass Spectrometry Microtubule-Associated Proteins - chemistry Microtubule-Associated Proteins - metabolism Microtubules Mitosis Mitosis - genetics Mitotic spindle apparatus Nuclear Proteins - genetics Nuclear Proteins - metabolism Protein Structure, Tertiary - genetics Protein-Serine-Threonine Kinases - chemistry Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Proteomics Small interfering RNA Spindle Apparatus - enzymology Spindle Apparatus - genetics Spindle Apparatus - ultrastructure Tubulin - chemistry Tubulin - metabolism |
| title | Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization |
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