Integrin-linked kinase associated with integrin activation
- 21 May 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 113 (21), 5304-5313
- https://doi.org/10.1182/blood-2008-07-169136
Abstract
Platelet integrin αIIbβ3 activation is tightly controlled by intracellular signaling pathways, and several molecules, including talin, have been identified as critical for αIIbβ3 activation. However, the whole pathway associated with αIIbβ3 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 αIIbα6Bβ3, and then obtained mutant cells expressing inactivated αIIbα6Bβ3 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 αIIbα6Bβ3. 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.This publication has 47 references indexed in Scilit:
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