T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T)

J Exp Med. 1993 Dec 1;178(6):2107-13. doi: 10.1084/jem.178.6.2107.

Abstract

Intracellular signaling from the T cell receptor (TCR)zeta/CD3 complex is likely to be mediated by associated protein tyrosine kinases such as p59fyn(T), ZAP-70, and the CD4:p56lck and CD8:p56lck coreceptors. The nature of the signaling cascade initiated by these kinases, their specificities, and downstream targets remain to be elucidated. The TCR-zeta/CD3:p59fyn(T) complex has previously been noted to coprecipitate a 120/130-kD doublet (p120/130). This intracellular protein of unknown identity associates directly with p59fyn(T) within the receptor complex. In this study, we have shown that this interaction with p120/130 is specifically mediated by the SH2 domain (not the fyn-SH3 domain) of p59fyn(T). Further, based on the results of in vitro kinase assays, p120/130 appears to be preferentially associated with p59fyn(T) in T cells, and not with p56lck. Antibody reprecipitation studies identified p120/130 as a previously described 130-kD substrate of pp60v-src whose function and structure is unknown. TCR-zeta/CD3 induced activation of T cells augmented the tyrosine phosphorylation of p120/130 in vivo as detected by antibody and GST:fyn-SH2 fusion proteins. p120/130 represents the first identified p59fyn(T):SH2 binding substrate in T cells, and as such is likely to play a key role in the early events of T cell activation.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • CD3 Complex / metabolism*
  • In Vitro Techniques
  • Macromolecular Substances
  • Membrane Proteins / metabolism*
  • Mice
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-fyn
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • CD3 Complex
  • Macromolecular Substances
  • Membrane Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Phosphotyrosine
  • Tyrosine
  • Receptor Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn