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J. Exp. Med.,
Volume 188, Number 3, August 3, 1998 561-575
Complex, Recruits Intracellular
Signaling Proteins to the Plasma Membrane
By


From the * Institute for Immunology and the The molecular mechanisms regulating recruitment of intracellular signaling proteins like
growth factor receptor-bound protein 2 (Grb2), phospholipase C
Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the § Protein and Peptide Group, European Molecular Biology Laboratories,
69117 Heidelberg, Germany; and the
Faculté de Médecine de Créteil, INSERM U448, 94010 Créteil Cedex, France
1, or phosphatidylinositol
3-kinase (PI3-kinase) to the plasma membrane after stimulation of the T cell receptor (TCR)-
CD3-
complex are not very well understood. We describe here purification, tandem mass
spectrometry sequencing, molecular cloning, and biochemical characterization of a novel transmembrane adaptor protein which associates and comodulates with the TCR-CD3-
complex
in human T lymphocytes and T cell lines. This protein was termed T cell receptor interacting
molecule (TRIM). TRIM is a disulfide-linked homodimer which is comprised of a short extracellular domain of 8 amino acids, a 19-amino acid transmembrane region, and a 159-amino
acid cytoplasmic tail. In its intracellular domain, TRIM contains several tyrosine-based signaling motifs that could be involved in SH2 domain-mediated protein-protein interactions. Indeed, after T cell activation, TRIM becomes rapidly phosphorylated on tyrosine residues and
then associates with the 85-kD regulatory subunit of PI3-kinase via an YxxM motif. Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in
targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR.
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