The AKT axis as a therapeutic target in autoimmune diseases

Endocrine, Metabolic and Immune Disorders - Drug Targets

Volumn 9, Issue 2, 2009, Pages 145-150

  Wu, Tianfu ^a   Mohan, Chandra ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EVEROLIMUS; PROTEIN KINASE B; RAPAMYCIN;

AUTOIMMUNE DISEASE; AUTOIMMUNITY; CANCER GROWTH; CELL GROWTH; CELL SURVIVAL; ENCEPHALOMYELITIS; GLUCOSE METABOLISM; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY DISEASE; LOW DRUG DOSE; LYMPHOCYTE PROLIFERATION; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; MULTIPLE SCLEROSIS; NONHUMAN; OSTEOARTHRITIS; PROTEIN EXPRESSION; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; ANIMAL; CELL PROLIFERATION; DRUG ANTAGONISM; MOUSE; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ARTHRITIS, RHEUMATOID; AUTOIMMUNE DISEASES; CELL PROLIFERATION; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MICE; MULTIPLE SCLEROSIS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 67650303113     PISSN: 18715303     EISSN: None     Source Type: Journal    
DOI: 10.2174/187153009788452417     Document Type: Review

References (54)

1. Goodnow, C.C.; Crosbie, J.; Adelstein, S.; Lavoie, T.B.; Smith-Gill, S.J.; Brink, R.A.; Pritchard-Briscoe, H.; Wotherspoon, J.S.; Loblay, R.H. and Raphael, K. (1988) Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature, 334(6184), 676-82.
2. Sakaguchi, S. (2005) Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol., 6(4), 345-352.
3. Matthews, R. (2007) Autoimmune diseases. The B cell slayer. Science, 318(5854), 1232-1233.
4. Zhu, J.; Liu, X.; Xie, C.; Yan, M.; Yu, Y.; Sobel, E.S.; Wakeland, E.K. and Mohan, C. (2005) T cell hyperactivity in lupus as a consequence of hyperstimulatory antigen-presenting cells. J. Clin. Invest., 115(7), 1869-1878.
5. Hur, E.M.; Youssef, S.; Haws, M.E.; Zhang, S.Y.; Sobel, R.A. and Steinman, L. (2007) Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat. Immunol., 8(1), 74-83.
6. Sinha, A.A.; Lopez, M.T. and McDevitt, H.O. (1990) Autoimmune diseases: the failure of self tolerance. Science, 248(4961), 1380-1388.
7. Summers, K.L.; O'Donnell, J.L.; Heiser, A.; Highton, J. and Hart, D.N. (1999) Synovial fluid transforming growth factor beta inhibits dendritic cell-T lymphocyte interactions in patients with chronic arthritis. Arthritis Rheum., 42(3), 507-518.
8. Hohlfeld, R.; Meinl, E. and Dornmair, K. (2008) B- and T-cell responses in multiple sclerosis: Novel approaches offer new insights. J. Neurol. Sci., 274(1-2), 5-8.
9. Prod'homme, T. and Zamvil, S.S. (2008) Bench to bedside: tempering antigen-presenting cells in multiple sclerosis. Nat. Med., 14(6), 614-615.
10. Chen, Y.; Kuchroo, V.K.; Inobe, J.; Hafler, D.A. and Weiner, H.L. (1994) Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science, 265(5176), 1237-40.
11. Liu, K.; Liang, C.; Liang, Z.; Tus, K. and Wakeland, E.K. (2005) Sle1ab mediates the aberrant activation of STAT3 and Ras-ERK signaling pathways in B lymphocytes. J. Immunol., 174(3), 1630-1637.
12. Kumar, K.R.; Li, L.; Yan, M.; Bhaskarabhatla, M.; Mobley, A.B.; Nguyen, C.; Mooney, J.M.; Schatzle, J.D.; Wakeland, E.K. and Mohan, C. (2006) Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science, 312(5780), 1665-1669.
13. Xie, C.; Patel, R.; Wu, T.; Zhu, J.; Henry, T.; Bhaskarabhatla, M.; Samudrala, R.; Tus, K.; Gong, Y.; Zhou, H.; Wakeland, E.K.; Zhou, X.J. and Mohan, C. (2007) PI3K/AKT/mTOR hypersignaling in autoimmune lymphoproliferative disease engendered by the epistatic interplay of Sle1b and FASlpr. Int. Immunol., 19(4), 509-522.
14. Wu, T.; Qin, X.; Kurepa, Z.; Kumar, K.R.; Liu, K.; Kanta, H.; Zhou, X.J.; Satterthwaite, A.B.; Davis, L.S. and Mohan, C. (2007) Shared signaling networks active in B cells isolated from genetically distinct mouse models of lupus. J. Clin. Invest., 117(8), 2186-2196.
15. Hutcheson, J.; Scatizzi, J.C.; Siddiqui, A.M.; Haines, G.K., 3rd; Wu, T.; Li, Q.Z.; Davis, L.S.; Mohan, C. and Perlman, H. (2008) Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. Immunity, 28(2), 206-217.
16. Coffer, P.J. and Woodgett, J.R. (1991) Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families. Eur. J. Biochem., 201(2), 475-481.
17. Brazil, D.P.; Yang, Z.Z. and Hemmings, B.A. (2004) Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem. Sci., 29(5), 233-242.
18. Brazil, D.P.; Park, J. and Hemmings, B.A. (2002) PKB binding proteins. Getting in on the Akt. Cell, 111(3), 293-303.
19. Cantley, L.C. (2002) The phosphoinositide 3-kinase pathway. Science, 296(5573), 1655-1657.
20. Shiojima, I. and Walsh, K. (2002) Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res., 90(12), 1243-1250.
21. Vivanco, I. and Sawyers, C.L. (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer, 2(7), 489-501.
22. Woodgett, J.R. (2005) Recent advances in the protein kinase B signaling pathway. Curr. Opin. Cell Biol., 17(2), 150-157.
23. Dufour, C.; Holy, X. and Marie, P.J. (2008) Transforming growth factor-beta prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling. Am. J. Physiol. Endocrinol. Metab., 294(4), E794-E801.
24. Lindvall, J. and Islam, T.C. (2002) Interaction of Btk and Akt in B cell signaling. Biochem. Biophys. Res. Commun., 293(5), 1319-1326.
25. Fujiwara, H.; Yamakuni, T.; Ueno, M.; Ishizuka, M.; Shinkawa, T.; Isobe, T. and Ohizumi, Y. (2004) IC101 induces apoptosis by Akt dephosphorylation via an inhibition of heat shock protein 90-ATP binding activity accompanied by preventing the interaction with Akt in L1210 cells. J. Pharmacol. Exp. Ther., 310(3), 1288-1295.
26. Jones, R.G.; Saibil, S.D.; Pun, J.M.; Elford, A.R.; Bonnard, M.; Pellegrini, M.; Arya, S.; Parsons, M.E.; Krawczyk, C.M.; Gerondakis, S.; Yeh, W.C.; Woodgett, J.R.; Boothby, M.R. and Ohashi, P.S. (2005) NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J. Immunol., 175(6), 3790-3799.
27. Yang, Z.Z.; Tschopp, O.; Baudry, A.; Dummler, B.; Hynx, D. and Hemmings, B.A. (2004) Physiological functions of protein kinase B/Akt. Biochem. Soc. Trans., 32(Pt 2), 350-354.
28. Parsons, M.J.; Jones, R.G.; Tsao, M.S.; Odermatt, B.; Ohashi, P.S. and Woodgett, J.R. (2001) Expression of active protein kinase B in T cells perturbs both T and B cell homeostasis and promotes inflammation. J. Immunol., 167(1), 42-48.
29. Coplon, N.S.; Diskin, C.J.; Petersen, J. and Swenson, R.S. (1983) The long-term clinical course of systemic lupus erythematosus in end-stage renal disease. N. Engl. J. Med., 308(4), 186-190.
30. Waldman, M. and Madaio, M.P. (2005) Pathogenic autoantibodies in lupus nephritis. Lupus, 14(1), 19-24.
31. Di Cristofano, A.; Kotsi, P.; Peng, Y.F.; Cordon-Cardo, C.; Elkon, K.B. and Pandolfi, P.P. (1999) Impaired Fas response and autoimmunity in Pten+/- mice. Science, 285(5436), 2122-2125.
32. Borlado, L.R.; Redondo, C.; Alvarez, B.; Jimenez, C.; Criado, L.M.; Flores, J.; Marcos, M.A.; Martinez, A.C.; Balomenos, D. and Carrera, A.C. (2000) Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo. FASEB J., 14(7), 895-903.
33. Barber,D.F.; Bartolome, A.; Hernandez, C.; Flores, J.M.; Redondo, C.; Fernandez-Arias, C.; Camps, M.; Ruckle, T.; Schwarz, M.K.; Rodriguez, S.; Martinez, A.C.; Balomenos, D.; Rommel, C. and Carrera, A.C. (2005) PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat. Med., 11(9), 933-935.
34. Kramer, S.; Kron, S.; Wang-Rosenke, Y.; Loof, T.; Khadzhynov, D.; Morgera, S.; Kawachi, H.; Shimizu, F.; Martini, S.; Neumayer, H.H. and Peters, H. (2008) Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative glomerulosclerosis. Am. J. Physiol. Renal. Physiol., 294(4), F801-F811.
35. Zhang, H.G.; Wang, Y.; Xie, J.F.; Liang, X.; Liu, D.; Yang, P.; Hsu, H.C.; Ray, R.B. and Mountz, J.D. (2001) Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt. Arthritis Rheum., 44(7), 1555-1567.
36. Hashiramoto, A.; Sakai, C.; Yoshida, K.; Tsumiyama, K.; Miura, Y.; Shiozawa, K.; Nose, M.; Komai, K. and Shiozawa, S. (2007) Angiopoietin 1 directly induces destruction of the rheumatoid joint by cooperative, but independent, signaling via ERK/MAPK and phosphatidylinositol 3-kinase/Akt. Arthritis Rheum., 56(7), 2170-2179.
37. Volin, M.V.; Huynh, N.; Klosowska, K.; Chong, K.K. and Woods, J.M. (2007) Fractalkine is a novel chemoattractant for rheumatoid arthritis fibroblast-like synoviocyte signaling through MAP kinases and Akt. Arthritis Rheum., 56(8), 2512-2522.
38. Liagre, B.; Vergne-Salle, P.; Leger, D.Y. and Beneytout, J.L. (2007) Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2. Int. J. Mol. Med., 20(4), 451-460.
39. Xu, H.; He, Y.; Yang, X.; Liang, L.; Zhan, Z.; Ye, Y.; Lian, F. and Sun, L. (2007) Anti-malarial agent artesunate inhibits TNF-alpha-induced production of proinflammatory cytokines via inhibition of NF-kappaB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology (Oxford), 46(6), 920-926.
40. Kim, G.; Jun, J.B. and Elkon, K.B. (2002) Necessary role of phosphatidylinositol 3-kinase in transforming growth factor beta-mediated activation of Akt in normal and rheumatoid arthritis synovial fibroblasts. Arthritis Rheum., 46(6), 1504-1511.
41. Noseworthy, J.H.; Lucchinetti, C.; Rodriguez, M. and Weinshenker, B.G. (2000) Multiple sclerosis. N. Engl. J. Med., 343(13), 938-952.
42. Dyment, D.A. and Ebers, G.C. (2002) An array of sunshine in multiple sclerosis. N. Engl. J. Med., 347(18), 1445-1447.
43. Hafler, D.A. (2004) Multiple sclerosis. J. Clin. Invest., 113(6), 788-794.
44. Quinones, M.P.; Kalkonde, Y.; Estrada, C.A.; Jimenez, F.; Ramirez, R.; Mahimainathan, L.; Mummidi, S.; Choudhury, G.G.; Martinez, H.; Adams, L.; Mack, M.; Reddick, R.L.; Maffi, S.; Haralambous, S.; Probert, L.; Ahuja, S.K. and Ahuja, S.S. (2008) Role of astrocytes and chemokine systems in acute TNFalpha induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-kappaB and Akt. Mol. Cell. Neurosci., 37(1), 96-109.
45. Takano, R.; Hisahara, S.; Namikawa, K.; Kiyama, H.; Okano, H. and Miura, M. (2000) Nerve growth factor protects oligodendrocytes from tumor necrosis factor-alpha-induced injury through Akt-mediated signaling mechanisms. J. Biol. Chem., 275(21), 16360-16365.
46. Barca, O.; Ferre, S.; Seoane, M.; Prieto, J.M.; Lema, M.; Senaris, R. and Arce, V.M. (2003) Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase. J. Neuroimmunol., 139(1-2), 155-159.
47. Martel, R.R.; Klicius, J. and Galet, S. (1977) Inhibition of the immune response by rapamycin, a new antifungal antibiotic. Can. J. Physiol. Pharmacol., 55(1), 48-51.
48. Branisteanu, D.D.; Mathieu, C. and Bouillon, R. (1997) Synergism between sirolimus and 1,25-dihydroxyvitamin D3 in vitro and in vivo. J. Neuroimmunol., 79(2), 138-147.
49. Graumann, U.; Reynolds, R.; Steck, A.J. and Schaeren-Wiemers, N. (2003) Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult. Brain Pathol., 13(4), 554-573.
50. Thirone, A.C.; Scarlett, J.A.; Gasparetti, A.L.; Araujo, E.P.; Lima, M.H.; Carvalho, C.R.; Velloso, L.A. and Saad, M.J. (2002) Modulation of growth hormone signal transduction in kidneys of streptozotocin-induced diabetic animals: effect of a growth hormone receptor antagonist. Diabetes, 51(7), 2270-2281.
51. Huisamen, B.; van Zyl, M.; Keyser, A. and Lochner, A. (2001) The effects of insulin and beta-adrenergic stimulation on glucose transport, glut 4 and PKB activation in the myocardium of lean and obese non-insulin dependent diabetes mellitus rats. Mol. Cell Biochem., 223(1-2), 15-25.
52. Dimmeler, S.; Fleming, I.; Fisslthaler, B.; Hermann, C.; Busse, R. and Zeiher, A.M. (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature, 399(6736), 601-605.
53. Liu, A.H.; Cao, Y.N.; Liu, H.T.; Zhang, W.W.; Liu, Y.; Shi, T.W.; Jia, G.L. and Wang, X.M. (2008) DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation. Cell Physiol. Biochem., 22(1-4), 177-186.
54. Li, J.; Zhang, H.; Wu, F.; Nan, Y.; Ma, H.; Guo, W.; Wang, H.; Ren, J.; Das, U.N. and Gao, F. (2008) Insulin inhibits tumor necrosis factor-alpha induction in myocardial ischemia/reperfusion: role of Akt and endothelial nitric oxide synthase phosphorylation. Crit. Care Med., 36(5), 1551-1558.