Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn.
Considerable evidence supports the hypothesis that the nonreceptor protein tyrosine kinase p59fyn participates in signal transduction from the T cell receptor (TCR). To examine this hypothesis in detail, we have produced mice that lack the thymic isoform of p59fyn but retain expression of the brain isoform of the protein. fynTnull mice exhibit a remarkably specific lymphoid defect: thymocytes are refractile to stimulation through the TCR with mitogen or antigen, while peripheral T cells, following what appears to be a normal maturation sequence, reacquire significant signaling capabilities. These data confirm that p59fynT plays a pivotal role in TCR signal transduction and demonstrate that additional developmentally regulated signaling components also contribute to TCR-induced lymphocyte activation.
Appleby
M W
MW
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Gross
J A
JA
Cooke
M P
MP
Levin
S D
SD
Qian
X
X
Perlmutter
R M
RM
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D002118:Calcium