Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2

Journal of Clinical Investigation

Volumn 113, Issue 3, 2004, Pages 441-450

  Woulfe, Donna ^a,b   Jiang, Hong ^a   Morgans, Alicia ^a   Monks, Robert ^a   Birnbaum, Morris ^a   Brass, Lawrence F ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBRINOGEN; G PROTEIN COUPLED RECEPTOR; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE; THROMBIN; THROMBOXANE A2; AKT2 PROTEIN, MOUSE; ISOPROTEIN; MESSENGER RNA; ONCOPROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM CELL LEVEL; CONTROLLED STUDY; EFFECTOR CELL; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; GENE DELETION; HEMOSTASIS; MEDIATOR RELEASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN STABILITY; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOCYTE RELEASE REACTION; THROMBOGENESIS; ANIMAL; BLEEDING TIME; BLOOD CLOTTING; GENETICS; METABOLISM; PHYSIOLOGY; THROMBOCYTE; THROMBOSIS;

ANIMALS; BLEEDING TIME; BLOOD COAGULATION; BLOOD PLATELETS; FIBRINOGEN; MICE; PLATELET ACTIVATION; PLATELET AGGREGATION; PROTEIN ISOFORMS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RNA, MESSENGER; THROMBOSIS;

EID: 1542317617     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI200420267     Document Type: Article

References (37)

1. Trumel, C., et al. 1999. A key role of adenosine diphosphate in the irreversible platelet aggregation induced by the PARI-activating peptide through the late activation of phosphoinositide 3-kinase. Blood. 94:4156-4165.
2. Kim, S., et al. 2002. Protease-activated receptors 1 and 4 do not stimulate G(i) signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of G(i) signaling. Blood. 99:3629-3636.
3. Dangelmaier, C., Jin, J., Smith, J.B., and Kunapuli, S.P. 2001. Potentiation of thromboxane A2-induced platelet secretion by Gi signaling through the phosphoinositide-3 kinase pathway. Thromb. Haemost. 85:341-348.
4. Jantzen, H.-M., Milstone, D.S., Gousset, L., Conley, P.B., and Mortensen, R.M. 2001. Impaired activation of murine platelets lacking G alpha(i2). J. Clin. Invest. 108:477-483. doi:10.1172/JCI200112818.
5. Li, Z., et al. 2003. Two waves of platelet secretion induced by thromboxane A2 receptor and a critical role for phosphoinositide 3-kinases. J. Biol. Chem. 278:30725-30731.
6. Kovacsovics, T.J., et al: 1995. Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation. J. Biol. Chem. 270:11358-11366.
7. Kucera, G.L., and Rittenhouse, S.E. 1990. Human platelets form 3-phosphorylated phosphoinositides in response to α-thrombin, U46619, or GTP gamma S. J. Biol. Chem. 265:5345-5348.
8. Zhang, J., Shattil, S.J., Cunningham, M.C., and Rittenhouse, S.E. 1996. Phosphoinositide 3-kinase gamma and p85/phosphoinositide 3-kinase in platelets. Relative activation by thrombin receptor or beta-phorbol myristate acetate and roles in promoting the ligand-binding function of αIIbβ3 integrin. J. Biol. Chem. 271:6265-6272.
9. Sultan, C., et al. 1991. Involvement of platelet glycoprotein IIb-IIIa (α IIb-β3 integrin) in thrombin-induced synthesis of phosphatidylinositol 3′,4′-bisphosphate. J. Biol. Chem. 266:23554-23557.
10. Sorisky, A., King, W.G., and Rittenhouse, S.E. 1992. Accumulation of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in thrombin-stimulated platelets. Different sensitivities to Ca2+ or functional integrin. Biochem. J. 286:581-584.
11. Banfic, H., et al. 1998. A novel integrin-activated pathway forms PKB/Akt-stimulatory phosphatidylinositol 3,4-bisphosphate via phosphatidylinositol 3-phosphate in platelets. J. Biol. Chem. 273:13-16.
12. Cantley, L.C. 2002. The phosphoinositide 3-kinase pathway. Science. 296:1655-1657.
13. Brazil, D.P., Park, J., and Hemmings, B.A. 2002. PKB binding proteins. Getting in on the Akt. Cell. 111:293-303.
14. Kroner, C., Eybrechts, K., and Akkerman, J.W. 2000. Dual regulation of platelet protein kinase B. J. Biol. Chem. 275:27790-27798.
15. Hirsch, E., et al. 2001. Resistance to thromboembolism in PI3Kγ-deficient mice. FASEB J. 15:2019-2021.
16. Lawlor, MA. 2001. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J. Cell Sci. 114:2903-2910.
17. Cho, H., Thorvaldsen, J.L., Chu, Q., Feng, F., and Birnbaum, M.J. 2001. Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276:38349-38352.
18. Cho, H., et al. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. 292:1728-1731.
19. Offermanns, S., Toombs, C.F., Hu, Y.H., and Simon, M.I. 1997. Defective platelet activation in G α(q)-deficient mice. Nature. 389:183-186.
20. Woulfe, D., Jiang, H., Mortensen, R., Yang, J., and Brass, L.F. 2002. Activation of Rap1B by G(i) family members in platelets. J. Biol. Chem. 277:23382-23390.
21. Kufrin, D., et al. 2003. Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets. Blood. 102:926-933.
22. Bellacosa, A., et al. 1998. Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene. 17:313-325.
23. Lova, P., et al. 2003. A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B. J. Biol. Chem. 278:131-138.
24. Peng, X.D., et al. 2003. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 17:1352-1365.
25. Vivanco, I., and Sawyers, C.L. 2002. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer. 2:489-501.
26. Altomare, D.A., Lyons, G.E., Mitsuuchi, Y., Cheng, J.Q., and Testa, J. R. 1998. Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Oncogene. 16:2407-2411.
27. Altomare, D.A., et al. 1995. Cloning, chromosomal localization and expression analysis of the mouse Akt2 oncogene. Oncogene. 11:1055-1060.
28. Garofalo, R.S., et al. 2003. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ J. Clin. Invest. 112:197-208. doi:10.1172/JCI200316885.
29. Nakatani, K., et al. 1999. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J. Biol. Chem. 274:21528-21532.
30. Banfic, H., Downes, C.P., and Rittenhouse, S.E. 1998. Biphasic activation of PKBalpha/Akt in platelets. Evidence for stimulation both by phosphatidylinositol 3,4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 273:11630-11637.
31. Barry, F.A., and Gibbins, J.M. 2002. Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI. J. Biol. Chem. 277:12874-12878.
32. Baurand, A., et al. 2000. Desensitization of the platelet aggregation response to ADP: differential down-regulation of the P2Y1 and P2cyc receptors. Thromb. Haemost. 84:484-491.
33. Hollopeter, G., et al. 2001. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 409:202-207.
34. Andre, P., et al. 2003. P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J. Clin. Invest. 112:398-406. doi:10.1172/JCI200317864.
35. Storey, R.F., et al. 2000. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br. J. Haematol. 110:925-934.
36. Paul, B.Z., Jin, J., and Kunapuli, S.P. 1999. Molecular mechanism of thromboxane A(2)-induced platelet aggregation. Essential role for p2t(ac) and alpha(2a) receptors. J. Biol. Chem. 274:29108-29114.
37. Watanabe, N., et al. 2003. Functional phenotype of phosphoinositide 3-kinase p85α-null platelets characterized by an impaired response to GP VI stimulation. Blood. 102:541-548.