Extracellular signal-regulated kinase (ERK) activation by the pre-T cell receptor in developing thymocytes in vivo.
The first checkpoint in T cell development occurs between the CD4(-)CD8(-) and CD4(+)CD8(+) stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal-regulated kinases (ERKs)-1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo.
Michie
A M
AM
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Trop
S
S
Wiest
D L
DL
Zúñiga-Pflücker
J C
JC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D013945:Thymoma / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases