Itk and Fyn make independent contributions to T cell activation.
Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.
Liao
X C
XC
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.
Littman
D R
DR
Weiss
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000502:physiology; D002455:Cell Division; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C080813:emt protein-tyrosine kinase