Integrin Linked Kinase Is Important in Platelet Signalling and Function.

Integrin linked kinase (ILK) is a 59 kDa protein that has been previously implicated in both collagen- and thrombin-induced platelet activation. Platelet stimulation results in the transient activation of ILK kinase activity and movement to the plasma membrane where signaling complexes are formed with beta 1 and beta 3 integrins. The change in ILK activity and association with beta 1 and beta 3 integrins that occurs upon stimulation suggests that this protein may be important for the co-ordination of platelet responses. We have successfully developed a conditional ILK knockout mouse model using the Cre-Lox system to enable the study of platelets deficient in this protein. ILK deficient mice appear healthy and have normal platelet levels by day 8 following induction of gene deletion. ILK deficient platelets display reduced aggregation and fibrinogen binding in response to agonists such as collagen and thrombin. This is accompanied by a secretion defect, although early collagen stimulated signaling such as PLCγ2 phosphorylation and calcium mobilization are unaffected. Analysis of blood from ILK deficient mice using an in vitro flow system showed reduced thrombus formation under arterial conditions. Furthermore, extended bleeding times were observed in these mice. The data presented here demonstrates that ILK has a role in platelet regulation and is important for functional haemostasis.