Lck dependence of signaling pathways activated by gamma-irradiation and CD3 epsilon engagement in RAG-1(-/-)-immature thymocytes.
The src family tyrosine kinase, Lck, transduces signals from the pre-TCR complex which regulate the development and expansion of CD4/CD8 double-positive (DP) thymocytes from CD25(+) CD4/CD8 double-negative progenitors. We and others have recently shown that sublethal gamma-irradiation bypasses the need for TCRbeta expression to promote the development and expansion of DP thymocytes in scid or recombinase-activating gene (RAG)-deficient mice. Here we demonstrate that gamma-irradiation activates an Lck-dependent signaling process in immature thymocytes similar to that initiated physiologically by the pre-TCR complex.
Wu
G
G
Wellesley Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada.
Danska
J S
JS
Guidos
C J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D005720:Gamma Rays; D018398:Homeodomain Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000235:genetics* / Q000528:radiation effects; D011828:Radiation Chimera / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D018398:Homeodomain Proteins; D011506:Proteins; C064658:RAG-1 protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases