Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways.
Activation of the T-cell receptor (TCR) and that of the B-cell receptor (BCR) elicits tyrosine-phosphorylation of proteins that belongs to similar functional categories, but result in distinct cellular responses. Large-scale analyses providing an overview of the signaling pathways downstream of TCR or BCR have not been described, so it has been unclear what components of these pathways are shared and which are specific. We have now performed a systematic analysis and provide a comprehensive list of tyrosine-phosphorylated proteins (PY proteome) with quantitative data on their abundance in T cell, B cell, and nonlymphoid cell lines. Our results led to the identification of novel tyrosine-phosphorylated proteins and signaling pathways not previously implicated in immunoreceptor signal transduction, such as clathrin, zonula occludens 2, eukaryotic translation initiation factor 3, and RhoH, suggesting that TCR or BCR signaling may be linked to downstream processes such as endocytosis, cell adhesion, and translation. Thus comparative and quantitative studies of tyrosine-phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level.
Matsumoto
Masaki
M
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan.
Oyamada
Koji
K
Takahashi
Hidehisa
H
Sato
Takamichi
T
Hatakeyama
Shigetsugu
S
Nakayama
Keiichi I
KI
D000941:Antigens / Q000276:immunology; D002448:Cell Adhesion; D002460:Cell Line; D002846:Chromatography, Affinity; D004705:Endocytosis; D006801:Humans; D019000:Phosphotyrosine / Q000032:analysis* / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000941:Antigens; D020543:Proteome; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D020741:rho GTP-Binding Proteins