CAST, a novel CD3epsilon-binding protein transducing activation signal for interleukin-2 production in T cells

J Biol Chem. 1999 Jun 25;274(26):18173-80. doi: 10.1074/jbc.274.26.18173.

Abstract

Antigen recognition through T cell receptor (TCR)-CD3 complex transduces signals into T cells, which regulate activation, function, and differentiation of T cells. The TCR-CD3 complex is composed of two signaling modules represented by CD3zeta and CD3epsilon. Signaling through CD3zeta has been extensively analyzed, but that via CD3epsilon, which is also crucial in immature thymocyte development, is still not clearly understood. We isolated cDNA encoding a novel CD3epsilon-binding protein CAST. CAST specifically interacts in vivo and in vitro with CD3epsilon but not with CD3zeta or FcRgamma via a unique membrane-proximal region of CD3epsilon. CAST is composed of 512 amino acids including a single tyrosine and undergoes tyrosine phosphorylation upon TCR stimulation. Overexpression of two dominant-negative types of CAST, a minimum CD3epsilon-binding domain and a tyrosine-mutant, strongly suppressed NFAT activation and interleukin-2 production. These results demonstrate that CAST serves as a component of preformed TCR complex and transduces activation signals upon TCR stimulation and represents a new signaling pathway via the CD3epsilon-containing TCR signaling module.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CD3 Complex*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / physiology*
  • DNA, Complementary / chemistry
  • Humans
  • Interleukin-2 / biosynthesis*
  • Intracellular Signaling Peptides and Proteins*
  • Jurkat Cells
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes / metabolism*
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • CD3 Complex
  • CD3E protein, human
  • Carrier Proteins
  • DNA, Complementary
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, T-Cell
  • Tyrosine
  • POLR1G protein, human

Associated data

  • GENBANK/AF017633