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

Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7493-8. doi: 10.1073/pnas.94.14.7493.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FYB1 protein, human
  • Interleukin-2
  • Membrane Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • antigen T cell receptor, zeta chain
  • Protein-Tyrosine Kinases
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn

Associated data

  • GENBANK/AF001862
  • GENBANK/AF001863