Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn)

Cell. 1991 Apr 19;65(2):281-91. doi: 10.1016/0092-8674(91)90162-r.


Engagement of the clonotypic antigen receptor (TCR) on T lymphocytes provokes an activation response leading to cell proliferation and lymphokine secretion. To examine the molecular basis of T cell signaling, we generated transgenic animals in which a lymphocyte-specific nonreceptor protein-tyrosine kinase p59fyn(T) is 20-fold overexpressed in developing T lineage cells. Thymocytes from these mice, analyzed using both cellular and biochemical assays, were remarkably hyperstimulable. Moreover, the responsiveness of normal thymocytes to TCR-derived signals correlated well with the extent to which p59fyn was expressed in these cells. Overexpression of a catalytically inactive form of p59fyn substantially inhibited TCR-mediated activation in otherwise normal thymocytes. These effects are unique to p59fyn; overexpression of a closely related T cell-specific tyrosine kinase, p56lck, elicits dramatically different phenotypes. Our results suggest that p59fyn is a critically important component of the TCR signal transduction apparatus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Calcium / metabolism
  • Cells, Cultured
  • Genetic Vectors
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Oncogene Protein pp60(v-src) / metabolism*
  • Phenotype
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-fyn
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology


  • Antigens, Differentiation, T-Lymphocyte
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • FYN protein, human
  • Fyn protein, mouse
  • Oncogene Protein pp60(v-src)
  • Proto-Oncogene Proteins c-fyn
  • Calcium