T-CELL RECEPTOR (TCR) INTERACTING MOLECULE (TRIM), A NOVEL DISULFIDE-LINKED DIMER ASSOCIATED WITH THE TCR-CD3-ZETA COMPLEX, RECRUITS INTRACELLULAR SIGNALING PROTEINS TO THE PLASMA-MEMBRANE

The molecular mechanisms regulating recruitment of intracellular signa ling proteins like growth factor receptor-bound protein 2 (Grb2), phos pholipase C gamma 1, or phosphatidylinositol 3-kinase (PI3-kinase) to the plasma membrane after stimulation of the T cell receptor (TCR)-CD3 -zeta; complex are not very well understood. We describe here purifica tion, tandem mass spectrometry sequencing, molecular cloning, and bioc hemical characterization of a novel trans membrane adaptor protein whi ch associates and comodulates with the TCR-CD3-zeta 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 whi ch is comprised of a short extracellular domain of 8 amino acids, a 19 -amino acid transmembrane region, and a 159-amino acid cytoplasmic tai l. In its intracellular domain, TRIM contains several tyrosine-based s ignaling motifs that could be involved in SH2 domain-mediated protein- protein interactions. Indeed, after T cell activation, TRIM becomes ra pidly 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 lik ely involved in targeting of intracellular signaling proteins to the p lasma membrane after triggering of the TCR.