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

Tucker, K. L., Sage, T., Stevens, J. M., Jordan, P. A., Jones, S., Barrett, N. E. ORCID: https://orcid.org/0000-0001-9123-1100, St-Arnaud, R., Frampton, J., Dedhar, S. and Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 (2008) A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood, 112 (12). pp. 4523-4531. ISSN 0006-4971 doi: 10.1182/blood-2008-03-148502

Abstract/Summary

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 coordination 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 ultrastructure 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 signaling such as PLC gamma 2 phosphorylation and calcium mobilization 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. (Blood. 2008; 112: 4523-4531)