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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4523-4531.
Prepublished online as a Blood First Edition Paper on September 4, 2008; DOI 10.1182/blood-2008-03-148502.


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Submitted March 28, 2008
Accepted August 11, 2008

A dual role for integrin linked kinase in platelets: regulating integrin function and {alpha}-granule secretion

Katherine L Tucker*, Tanya Sage, Joanne M Stevens, Peter A Jordan, Sarah Jones, Natasha E Barrett, Rene St-Arnaud, Jonathan Frampton, Shoukat Dedhar, and Jonathan M Gibbins

School of Biological Sciences, The University of Reading, Reading, United Kingdom
Department of Surgery and Department of Human Genetics, McGill University, Montreal, Quebec, Canada
Division of Immunity and Infection, Birmingham University Medical School, Birmingham, United Kingdom
Cancer Genetics and Developmental Biology, The BC Cancer Research Centre, Vancouver, British Columbia, Canada

* Corresponding author; email: k.l.tucker{at}rdg.ac.uk.

Integrin linked kinase (ILK) has been implicated in the regulation of a range of fundamental biological processes such as cell survival, growth, differentiation and adhesion. In platelets ILK associates with {beta}1 and {beta}3 containing integrins, which are of paramount importance for the function of platelets. Upon stimulation of platelets this association with the integrins is increased and ILK kinase activity is up-regulated, suggesting that ILK may be important for the co-ordination of platelet responses. In this study a conditional knockout mouse model was developed to examine the role of ILK in platelets. The ILK-deficient mice showed an increased bleeding time and volume, and despite normal ultra structure the function of ILK-deficient platelets was decreased significantly. This included reduced aggregation, fibrinogen binding and thrombus formation under arterial flow conditions. Furthermore, although early collagen stimulated signalling such as PLC{gamma}2 phosphorylation and calcium mobilisation were unaffected in ILK-deficient platelets, a selective defect in {alpha}-granule, but not dense-granule, secretion was observed. These results indicate that as well as involvement in the control of integrin affinity, ILK is required for {alpha}-granule secretion and therefore may play a central role in the regulation of platelet function.


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