Fyn can partially substitute for Lck in T lymphocyte development.
Lck, a Src family tyrosine kinase, transduces signals important for the development of alphabeta and gammadelta T cells. However, T cell development is only partially compromised in Lck-deficient mice, suggesting that other kinases may also transduce pre-TCR or TCR signals. One candidate is Fyn, a Src kinase coexpressed with Lck in immature and mature T cells. Here we show that T cell development is completely compromised in lck(-/-)fyn(-/-) mice. In addition, we demonstrate that expression of a gain-of-function mutant fyn(T) transgene completely restores production of immature CD4/CD8 double positive thymocytes and gammadelta T cells and improves the representation of CD4 or CD8 single positive thymocytes. These observations reveal that Fyn can subserve some Lck-like functions in T cell development.
Groves
T
T
Division of Immunology and Cancer, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Smiley
P
P
Cooke
M P
MP
Forbush
K
K
Perlmutter
R M
RM
Guidos
C J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008817:Mice, Mutant Strains; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D051076:Proto-Oncogene Proteins c-fyn; D013601:T-Lymphocytes / Q000276:immunology*; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology*
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases