| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Pathway1
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697
T cells resistant to the immunosuppressive drug cyclosporin A (CsA)
may be important mediators of chronic graft rejection. We previously
reported that T cells activated in the presence of endothelial cells
(EC) develop resistance to CsA, and initiate IL-2 secretion within
8–12 h of triggering. CsA normally blocks the phosphatase,
calcineurin, thus preventing nuclear translocation of the transcription
factor, NFAT. We find that in the presence but not the absence of EC,
NFAT1 can be detected in the nuclei of CsA-treated T cells within
8 h of triggering, reaching a maximal level of 60% of control by
24 h. Glycogen synthase kinase-3
(GSK-3), which
rephosphorylates NFAT and promotes nuclear export, is inhibited by EC
costimulation. GSK-3 is a component of the wnt signaling pathway,
and EC express wnt-5a and T cells express frizzled-5, a wnt-5a
receptor. Wnt-5a promotes T cell NFAT nuclear accumulation in the
presence of CsA, an effect mimicked by Li+, a potent
inhibitor of GSK-3. The protein kinase C agonist PMA dramatically
synergizes with both EC and wnt-5a in stimulating T cell IL-2
synthesis, and inhibition of either protein kinase C by Ro-31-8425 or
G-proteins by pertussis toxin effectively blocks the actions of wnt-5a
on T cells. Finally, a secreted, dominant-negative form of frizzled-5
blocks EC-mediated CsA resistance. Thus, EC promote CsA-resistant
nuclear localization of NFAT and subsequent IL-2 synthesis through a
noncanonical wnt-dependent pathway.
This article has been cited by other articles:
|
|
 |
|
  J. L. J. van der Velden, A. M. W. J. Schols, J. Willems, M. C. J. M. Kelders, and R. C. J. Langen Glycogen Synthase Kinase 3 Suppresses Myogenic Differentiation through Negative Regulation of NFATc3 J. Biol. Chem., January 4, 2008; 283(1): 358 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Dissanayake, M. Wade, C. E. Johnson, M. P. O'Connell, P. D. Leotlela, A. D. French, K. V. Shah, K. J. Hewitt, D. T. Rosenthal, F. E. Indig, et al. The Wnt5A/Protein Kinase C Pathway Mediates Motility in Melanoma Cells via the Inhibition of Metastasis Suppressors and Initiation of an Epithelial to Mesenchymal Transition J. Biol. Chem., June 8, 2007; 282(23): 17259 - 17271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tellides and J. S. Pober Interferon-{gamma} Axis in Graft Arteriosclerosis Circ. Res., March 16, 2007; 100(5): 622 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-S. Shi, N.-N. Huang, K. Harrison, S.-B. Han, and J. H. Kehrl The Mitogen-Activated Protein Kinase Kinase Kinase Kinase GCKR Positively Regulates Canonical and Noncanonical Wnt Signaling in B Lymphocytes. Mol. Cell. Biol., September 1, 2006; 26(17): 6511 - 6521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dejmek, A. Safholm, C. Kamp Nielsen, T. Andersson, and K. Leandersson Wnt-5a/Ca2+-Induced NFAT Activity Is Counteracted by Wnt-5a/Yes-Cdc42-Casein Kinase 1{alpha} Signaling in Human Mammary Epithelial Cells. Mol. Cell. Biol., August 1, 2006; 26(16): 6024 - 6036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Blumenthal, S. Ehlers, J. Lauber, J. Buer, C. Lange, T. Goldmann, H. Heine, E. Brandt, and N. Reiling The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation Blood, August 1, 2006; 108(3): 965 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wittmann, C. Killig, M. Bruder, R. Gutzmer, and T. Werfel Critical involvement of IL-12 in IFN-{gamma} induction by calcineurin antagonists in activated human lymphocytes J. Leukoc. Biol., July 1, 2006; 80(1): 75 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Reinhold, R. M. Kapadia, Z. Liao, and M. C. Naski The Wnt-inducible Transcription Factor Twist1 Inhibits Chondrogenesis J. Biol. Chem., January 20, 2006; 281(3): 1381 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Choi, J. Walker, K. Talbert-Slagle, P. Wright, J. S. Pober, and L. Alexander Endothelial Cells Promote Human Immunodeficiency Virus Replication in Nondividing Memory T Cells via Nef-, Vpr-, and T-Cell Receptor-Dependent Activation of NFAT J. Virol., September 1, 2005; 79(17): 11194 - 11204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wang, B. Lu, P. Wood, and R. D. Lund Grafting of ARPE-19 and Schwann Cells to the Subretinal Space in RCS Rats Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2552 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Komarova, A. Pereverzev, J. W. Shum, S. M. Sims, and S. J. Dixon Convergent signaling by acidosis and receptor activator of NF-{kappa}B ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts PNAS, February 15, 2005; 102(7): 2643 - 2648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Puri, B. S. Magenheimer, R. L. Maser, E. M. Ryan, C. A. Zien, D. D. Walker, D. P. Wallace, S. J. Hempson, and J. P. Calvet Polycystin-1 Activates the Calcineurin/NFAT (Nuclear Factor of Activated T-cells) Signaling Pathway J. Biol. Chem., December 31, 2004; 279(53): 55455 - 55464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kiani, I. Habermann, M. Haase, S. Feldmann, S. Boxberger, M. A. Sanchez-Fernandez, C. Thiede, M. Bornhauser, and G. Ehninger Expression and regulation of NFAT (nuclear factors of activated T cells) in human CD34+ cells: down-regulation upon myeloid differentiation J. Leukoc. Biol., November 1, 2004; 76(5): 1057 - 1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu, M. Holm, X.-Q. Xie, M. Wolf-Watz, and T. Grundstrom AML1/Runx1 Recruits Calcineurin to Regulate Granulocyte Macrophage Colony-stimulating Factor by Ets1 Activation J. Biol. Chem., July 9, 2004; 279(28): 29398 - 29408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lawrence, D. J. Keegan, E. M. Muir, P. J. Coffey, J. H. Rogers, M. J. Wilby, J. W. Fawcett, and R. D. Lund Transplantation of Schwann Cell Line Clones Secreting GDNF or BDNF into the Retinas of Dystrophic Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 267 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Gregory, H. Singh, A. S. Perry, and D. J. Prockop The Wnt Signaling Inhibitor Dickkopf-1 Is Required for Reentry into the Cell Cycle of Human Adult Stem Cells from Bone Marrow J. Biol. Chem., July 18, 2003; 278(30): 28067 - 28078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Neal and N. A. Clipstone A Constitutively Active NFATc1 Mutant Induces a Transformed Phenotype in 3T3-L1 Fibroblasts J. Biol. Chem., May 2, 2003; 278(19): 17246 - 17254. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
