1. A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion
- Author
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Joanne M. Stevens, Natasha E. Barrett, Peter A. Jordan, Jonathan M. Gibbins, Shoukat Dedhar, Katherine L. Tucker, Tanya Sage, Jonathan Frampton, René St-Arnaud, and Sarah Jones
- Subjects
Blood Platelets ,Platelet Aggregation ,Immunology ,Integrin ,Hemorrhage ,Platelet Glycoprotein GPIIb-IIIa Complex ,Protein Serine-Threonine Kinases ,Biology ,Hemostasis, Thrombosis, and Vascular Biology ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Platelet ,Integrin-linked kinase ,Platelet activation ,Cloning, Molecular ,protein-kinase cell-adhesion actin cytoskeleton ilk activation matrix pinch sites complex phosphorylation ,Kinase activity ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Cell adhesion molecule ,Secretory Vesicles ,Fibrinogen binding ,Thrombosis ,Cell Biology ,Hematology ,Platelet Activation ,3. Good health ,Cell biology ,Mice, Inbred C57BL ,030220 oncology & carcinogenesis ,embryonic structures ,biology.protein - Abstract
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)
- Published
- 2016