Integrin-linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi

Journal of Thrombosis and Haemostasis

Volumn 12, Issue 8, 2014, Pages 1342-1352

  Jones, C I ^a   Tucker, K L ^a,b   Sasikumar, P ^a   Sage, T ^a   Kaiser, W J ^a   Moore, C ^c   Emerson, M ^c   Gibbins, J M ^a  

^a UNIVERSITY OF READING   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Embolism; Integrin alpha IIb beta 3; Integrin linked kinase; Platelets; Thrombus

Indexed keywords

ADENOSINE DIPHOSPHATE; FIBRINOGEN; INTEGRIN LINKED KINASE; PADGEM PROTEIN; THROMBIN; FIBRINOGEN RECEPTOR; INTEGRIN-LINKED KINASE; PROTEIN SERINE THREONINE KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD CLOT RETRACTION; BLOOD CLOTTING; CONTROLLED STUDY; DEGRANULATION; ENZYME DEFICIENCY; ENZYME INHIBITION; FLOW CYTOMETRY; HEMOSTASIS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SECRETION; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOCYTE MEMBRANE; ANIMAL; ENZYMOLOGY; METABOLISM; THROMBOSIS; TRANSGENIC MOUSE;

ANIMALS; FLOW CYTOMETRY; MICE; MICE, TRANSGENIC; PLATELET ACTIVATION; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PROTEIN-SERINE-THREONINE KINASES; THROMBOSIS;

EID: 84905679657     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12620     Document Type: Article

References (37)

1. Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S. Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 1996; 379: 91-6.
2. Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J Biol Chem 2001; 276: 27462-9.
3. Dobreva I, Fielding A, Foster LJ, Dedhar S. Mapping the integrin-linked kinase interactome using SILAC. J Proteome Res 2008; 7: 1740-9.
4. Lange A, Wickstrom SA, Jakobson M, Zent R, Sainio K, Fassler R. Integrin-linked kinase is an adaptor with essential functions during mouse development. Nature 2009; 461: 1002-6.
5. Tu Y, Li F, Goicoechea S, Wu C. The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. Mol Cell Biol 1999; 19: 2425-34.
6. Li F, Zhang Y, Wu C. Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats. J Cell Sci 1999; 112(Pt 24): 4589-99.
7. Yamaji S, Suzuki A, Sugiyama Y, Koide Y, Yoshida M, Kanamori H, Mohri H, Ohno S, Ishigatsubo Y. A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction. J Cell Biol 2001; 153: 1251-64.
8. Zhang Y, Chen K, Tu Y, Wu C. Distinct roles of two structurally closely related focal adhesion proteins, alpha-parvins and beta-parvins, in regulation of cell morphology and survival. J Biol Chem 2004; 279: 41695-705.
9. Legate KR, Montanez E, Kudlacek O, Fassler R. ILK, PINCH and parvin: the tIPP of integrin signalling. Nat Rev Mol Cell Biol 2006; 7: 20-31.
10. McDonald PC, Oloumi A, Mills J, Dobreva I, Maidan M, Gray V, Wederell ED, Bally MB, Foster LJ, Dedhar S. Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival. Cancer Res 2008; 68: 1618-24.
11. Sakai T, Li S, Docheva D, Grashoff C, Sakai K, Kostka G, Braun A, Pfeifer A, Yurchenco PD, Fassler R. Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev 2003; 17: 926-40.
12. Stanchi F, Grashoff C, Nguemeni Yonga CF, Grall D, Fassler R, van Obberghen-Schilling E. Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation. J Cell Sci 2009; 122: 1800-11.
13. Friedrich EB, Liu E, Sinha S, Cook S, Milstone DS, MacRae CA, Mariotti M, Kuhlencordt PJ, Force T, Rosenzweig A, St-Arnaud R, Dedhar S, Gerszten RE. Integrin-linked kinase regulates endothelial cell survival and vascular development. Mol Cell Biol 2004; 24: 8134-44.
14. Tucker KL, Sage T, Stevens JM, Jordan PA, Jones S, Barrett NE, St-Arnaud R, Frampton J, Dedhar S, Gibbins JM. A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood 2008; 112: 4523-31.
15. White DE, Coutu P, Shi YF, Tardif JC, Nattel S, St Arnaud R, Dedhar S, Muller WJ. Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure. Genes Dev 2006; 20: 2355-60.
16. Gkretsi V, Bowen WC, Yang Y, Wu C, Michalopoulos GK. Integrin-linked kinase is involved in matrix-induced hepatocyte differentiation. Biochem Biophys Res Commun 2007; 353: 638-43.
17. Naska S, Park KJ, Hannigan GE, Dedhar S, Miller FD, Kaplan DR. An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth. J Neurosci 2006; 26: 13344-56.
18. Pasquet JM, Noury M, Nurden AT. Evidence that the platelet integrin alphaIIb beta3 is regulated by the integrin-linked kinase, ILK, in a PI3-kinase dependent pathway. Thromb Haemost 2002; 88: 115-22.
19. Stevens JM, Jordan PA, Sage T, Gibbins JM. The regulation of integrin-linked kinase in human platelets: evidence for involvement in the regulation of integrin alpha 2 beta 1. J Thromb Haemost 2004; 2: 1443-52.
20. Troussard AA, Mawji NM, Ong C, Mui A, St-Arnaud R, Dedhar S. Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation. J Biol Chem 2003; 278: 22374-8.
21. Spyridon M, Moraes LA, Jones CI, Sage T, Sasikumar P, Bucci G, Gibbins JM. LXR as a novel antithrombotic target. Blood 2011; 117: 5751-61.
22. Vaiyapuri S, Jones CI, Sasikumar P, Moraes LA, Munger SJ, Wright JR, Ali MS, Sage T, Kaiser WJ, Tucker KL, Stain CJ, Bye AP, Jones S, Oviedo-Orta E, Simon AM, Mahaut-Smith MP, Gibbins JM. Gap junctions and connexin hemichannels underpin hemostasis and thrombosis. Circulation 2012; 125: 2479-91.
23. Morton LF, Hargreaves PG, Farndale RW, Young RD, Barnes MJ. Integrin alpha 2 beta 1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for alpha 2 beta 1-independent platelet reactivity. Biochem J 1995; 306: 337-44.
24. Tymvios C, Jones S, Moore C, Pitchford SC, Page CP, Emerson M. Real-time measurement of non-lethal platelet thromboembolic responses in the anaesthetized mouse. Thromb Haemost 2008; 99: 435-40.
25. Troussard AA, McDonald PC, Wederell ED, Mawji NM, Filipenko NR, Gelmon KA, Kucab JE, Dunn SE, Emerman JT, Bally MB, Dedhar S. Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res 2006; 66: 393-403.
26. Yau CY, Wheeler JJ, Sutton KL, Hedley DW. Inhibition of integrin-linked kinase by a selective small molecule inhibitor, QLT0254, inhibits the PI3K/PKB/mTOR, Stat3, and FKHR pathways and tumor growth, and enhances gemcitabine-induced apoptosis in human orthotopic primary pancreatic cancer xenografts. Cancer Res 2005; 65: 1497-504.
27. Eke I, Leonhardt F, Storch K, Hehlgans S, Cordes N. The small molecule inhibitor QLT0267 radiosensitizes squamous cell carcinoma cells of the head and neck. PLoS One 2009; 4: e6434.
28. Cifuni SM, Wagner DD, Bergmeier W. CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets. Blood 2008; 112: 1696-703.
29. Stefanini L, Roden RC, Bergmeier W. CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 2009; 114: 2506-14.
30. Stolla M, Stefanini L, Roden RC, Chavez M, Hirsch J, Greene T, Ouellette TD, Maloney SF, Diamond SL, Poncz M, Woulfe DS, Bergmeier W. The kinetics of alphaIIbbeta3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy. Blood 2011; 117: 1005-13.
31. Honda S, Shirotani-Ikejima H, Tadokoro S, Maeda Y, Kinoshita T, Tomiyama Y, Miyata T. Integrin-linked kinase associated with integrin activation. Blood 2009; 113: 5304-13.
32. Wickstrom SA, Lange A, Montanez E, Fassler R. The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase! EMBO J 2010; 29: 281-91.
33. Fukuda K, Gupta S, Chen K, Wu C, Qin J. The pseudoactive site of ILK is essential for its binding to alpha-parvin and localization to focal adhesions. Mol Cell 2009; 36: 819-30.
34. Moik D, Bottcher A, Makhina T, Grashoff C, Bulus N, Zent R, Fassler R. Mutations in the paxillin-binding site of integrin-linked kinase (ILK) destabilize the pseudokinase domain and cause embryonic lethality in mice. J Biol Chem 2013; 288: 18863-71.
35. Kim YB, Choi S, Choi MC, Oh MA, Lee SA, Cho M, Mizuno K, Kim SH, Lee JW. Cell adhesion-dependent cofilin serine 3 phosphorylation by the integrin-linked kinase.c-Src complex. J Biol Chem 2008; 283: 10089-96.
36. Stefanini L, Boulaftali Y, Ouellette TD, Holinstat M, Desire L, Leblond B, Andre P, Conley PB, Bergmeier W. Rap1-Rac1 circuits potentiate platelet activation. Arterioscler Thromb Vasc Biol 2012; 32: 434-41.
37. Qadota H, Moerman DG, Benian GM. A molecular mechanism for the requirement of PAT-4 (integrin-linked kinase (ILK)) for the localization of UNC-112 (Kindlin) to integrin adhesion sites. J Biol Chem 2012; 287: 28537-51.