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J. Biol. Chem., Vol. 277, Issue 32, 28418-28423, August 9, 2002
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From the Polyunsaturated fatty acids (PUFAs) suppress
immune responses and inhibit T cell activation through largely unknown
mechanisms. The displacement of signaling proteins from membrane lipid
rafts has recently been suggested as underlying PUFA-mediated T cell inhibition. We show here that PUFA treatment specifically interferes with T cell signal transduction by blocking tyrosine phosphorylation of
LAT (linker for activation of T cells) and phospholipase C
LAT Displacement from Lipid Rafts as a Molecular Mechanism for
the Inhibition of T Cell Signaling by Polyunsaturated Fatty Acids*
,
ej
í¶,, and
Department of Internal Medicine III
and the § Institute of Immunology, University of Vienna,
A-1090 Vienna, Austria and the ¶ Institute of Molecular Genetics,
Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech
Republic
1. A
significant fraction of LAT was displaced from rafts by PUFA treatment
along with other signaling proteins. However, retaining LAT alone in
lipid rafts effectively restored phospholipase C1/calcium signaling
in PUFA-treated T cells. These data reveal LAT displacement from lipid
rafts as a molecular mechanism by which PUFAs inhibit T cell signaling
and underline the predominant importance of LAT localization in rafts
for efficient T cell activation.
*
This work was supported by Austrian Science Foundation Grant
P13507-Med (to T. M. S.), the Interdisciplinary Cooperation Project program of the Austrian Federal Ministry for Education, Science, and
Culture (to T. M. S. and W. W.), and Welcome Trust Grant J1116W24Z (to V. H.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
43-1-40400-4319; Fax: 43-1-40400-4845; E-mail:
thomas.stulnig@akh-wien.ac.at.
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