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Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production.

T cell receptor zeta (TcRzeta)/CD3 ligation initiates a signaling cascade that involves src kinases p56(lck) and zeta-associated protein 70, leading to the phosphorylation of substrates such as TcRzeta, Vav, SH2-domain-containing leukocyte protein 76 (SLP-76), cbl, and p120/130. FYN binding protein (FYB or p120/130) associates with p59(fyn), the TcRzeta/CD3 complex, and becomes tyrosine-phosphorylated in response to receptor ligation. In this study, we report the cDNA cloning of human and murine FYB and show that it is restricted in expression to T cells and myeloid cells and possesses an overall unique hydrophilic sequence with several tyrosine-based motifs, proline-based type I and type II SH3 domain binding motifs, several putative lysine/glutamic acid-rich nuclear localization motifs, and a SH3-like domain. In addition to binding the src kinase p59(fyn), FYB binds specifically to the hematopoietic signaling protein SLP-76, an interaction mediated by the SLP-76 SH2 domain. In keeping with this, expression of FYB augmented interleukin 2 secretion from a T cell hybridoma, DC27.10, in response to TcRzeta/CD3 ligation. FYB is therefore a novel hematopoietic protein that acts as a component of the FYN and SLP-76 signaling cascades in T cells.

Pubmed ID: 9207119


  • da Silva AJ
  • Li Z
  • de Vera C
  • Canto E
  • Findell P
  • Rudd CE


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 8, 1997

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Carrier Proteins
  • Cloning, Molecular
  • Humans
  • Interleukin-2
  • Jurkat Cells
  • Membrane Proteins
  • Molecular Sequence Data
  • Phosphoproteins
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes