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 signaling proteins like growth factor receptor-bound protein 2 (Grb2), phospholipase Cgamma1, 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 purification, tandem mass spectrometry sequencing, molecular cloning, and biochemical characterization of a novel transmembrane adaptor protein which 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 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.
Institute for Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
E
E
Bruyns
A
A
Marie-Cardine
H
H
Kirchgessner
K
K
Sagolla
A
A
Shevchenko
M
M
Mann
F
F
Autschbach
A
A
Bensussan
S
S
Meuer
B
B
Schraven
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D019281:Dimerization; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000378:metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D002352:Carrier Proteins; D018076:DNA, Complementary; D004220:Disulfides; D008565:Membrane Proteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C114030:TRAT1 protein, human; D014443:Tyrosine; D019061:src-Family Kinases