TY - JOUR
T1 - A dual role for integrin-linked kinase in platelets
T2 - regulating integrin function and alpha-granule secretion
AU - Tucker, K.L.
AU - Sage, T.
AU - Stevens, J.M.
AU - Jordan, P.A.
AU - Jones, S.
AU - Barrett, N.E.
AU - St-Arnaud, R.
AU - Frampton, J.
AU - Dedhar, S.
AU - Gibbins, J.M.
N1 - WOS:000261217000028
Times Cited: 18 Tucker, Katherine L. Sage, Tanya Stevens, Joanne M. Jordan, Peter A. Jones, Sarah Barrett, Natasha E. St-Arnaud, Rene Frampton, Jonathan Dedhar, Shoukat Gibbins, Jonathan M.
PY - 2008
Y1 - 2008
N2 - 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)
AB - 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)
KW - protein-kinase cell-adhesion actin cytoskeleton ilk activation matrix pinch sites complex phosphorylation
U2 - 10.1182/blood-2008-03-148502
DO - 10.1182/blood-2008-03-148502
M3 - Article
VL - 112
SP - 4523
EP - 4531
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -