The Journal of Experimental Medicine
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Published online 10 November 2003 doi:10.1084/jem.20031484
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© Rockefeller University Press, 0022-1007/2003/11/1453 $5.00
The Journal of Experimental Medicine, Volume 198, Number 10, 1453-1462

LIME : A New Membrane Raft-associated Adaptor Protein Involved in CD4 and CD8 Coreceptor Signaling



Nadezda Brdicková1, Tomás Brdicka1, Pavla Angelisová1, Ondrej Horváth1, Jirí Spicka1, Ivan Hilgert1, Jan Paces1, Luca Simeoni2, Stefanie Kliche2, Camilla Merten2, Burkhart Schraven2 and Václav Horejsí1

1 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic
2 Institute for Immunology, Otto-von-Guericke-University, 39120 Magdeburg, Germany

Address correspondence to Václav Horejsí, Institute of Molecular Genetics, AS CR, Vídenská 1083, 142 20 Praha 4, Czech Republic. Phone: 420-2-41729908; Fax: 420-2-44472282; email: horejsi{at}biomed.cas.cz; or Burkhart Schraven, Institute for Immunology, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany. Phone: 0391-67-15800; Fax: 0391-67-15852; email: burkhart.schraven{at}medizin.uni-magdeburg.de

Lymphocyte membrane rafts contain molecules critical for immunoreceptor signaling. Here, we report identification of a new raft-associated adaptor protein LIME (Lck-interacting molecule) expressed predominantly in T lymphocytes. LIME becomes tyrosine phosphorylated after cross-linking of the CD4 or CD8 coreceptors. Phospho-LIME associates with the Src family kinase Lck and its negative regulator, Csk. Ectopic expression of LIME in Jurkat T cells results in an increase of Csk in lipid rafts, increased phosphorylation of Lck and higher Ca2+ response to CD3 stimulation. Thus, LIME appears to be involved in regulation of T cell activation by coreceptors.

Key Words: membrane microdomains • Lck • Csk • signal transduction • phosphorylation


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