|
|
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles |
Complex, Recruits Intracellular Signaling Proteins to the Plasma Membrane
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
The molecular mechanisms regulating recruitment of intracellular signaling proteins like growth factor receptor–bound protein 2 (Grb2), phospholipase C
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.
Key Words: T lymphocytes • T cell receptor • transmembrane adaptor proteins
A. Marie-Cardine is a recipient of a fellowship from the Training and Mobility of Researchers program of the European Community (ERBFMBICT950472). This work was supported in part by the Deutsche Forschungs Gemeinschaft grants SCHR/533/1-1 and SFB 405/A5 (B. Schraven) and B9 (F. Autschbach). The work in M. Mann's laboratory was supported in part by a generous grant from the German Technology Ministry (BMBF).
M. Mann's present address is Center of Experimental Bioinformatics, Odense University, Staermosegaadsvej 16, DK-5230 Odense M, Denmark.
E. Bruyns, A. Marie-Cardine, and H. Kirchgessner contributed equally to this work.
Abbreviations used: Grb2, growth factor receptor–bound protein 2; GST, glutathione-S-transferase; IEF, isoelectric focussing; LAT, linker for activation of T cells; MAP, mitogen-activated protein; PI3-kinase, phosphatidylinositol 3-kinase; PTK, protein tyrosine kinase; PTYR, phosphotyrosine; RACE, rapid amplification of cDNA ends; SH2, src homology 2; SKAP55, src kinase–associated phosphoprotein of 55 kD; TRIM, T cell receptor interacting molecule(s).
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| TABLE OF CONTENTS |
|
