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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5304-5313. Prepublished online as a Blood First Edition Paper on March 18, 2009; DOI 10.1182/blood-2008-07-169136. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-169136v1 113/21/5304    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Honda, S. Articles by Miyata, T. Search for Related Content PubMed PubMed Citation Articles by Honda, S. Articles by Miyata, T. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Integrin-linked kinase associated with integrin activation Shigenori Honda1, Hiroko Shirotani-Ikejima1, Seiji Tadokoro2, Yusuke Maeda3, Taroh Kinoshita3, Yoshiaki Tomiyama2, and Toshiyuki Miyata1 1 National Cardiovascular Center Research Institute, Osaka; 2 Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka; and 3 Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Platelet integrin IIbβ3 activation is tightly controlled by intracellular signaling pathways, and several molecules, including talin, have been identified as critical for IIbβ3 activation. However, the whole pathway associated with IIbβ3 activation remains to be determined. To address this issue, we established a Chinese hamster ovary cell line (parental cells) that expresses constitutively activated chimeric integrin IIb6Bβ3, and then obtained mutant cells expressing inactivated IIb6Bβ3 by genome-wide mutagenesis. We have performed expression cloning to isolate signaling molecules responsible for integrin activation in the mutant cells. We show that integrin-linked kinase (ILK) complements defective integrin activation in the mutant cells. ILK mRNAs in the mutant cells contained 2 nonsense mutations, R317X and W383X, in a compound heterozygous state, resulting in a complete loss of ILK expression. Moreover, the mutant cells showed partially impaired activation of endogenous β1 integrins. Knockdown of ILK in parental cells significantly suppressed the activated state of IIb6Bβ3. However, ILK overexpression did not rescue the impaired integrin activation in talin knocked-down parental cells, whereas overexpression of talin-F3, a subdomain of the talin head domain, restored the function. Our present data suggest that ILK contributes to inside-out integrin activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. J. Conti, S. J. Monkley, M. R. Wood, D. R. Critchley, and U. Muller Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions Development, November 1, 2009; 136(21): 3597 - 3606. [Abstract] [Full Text] [PDF]

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