Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Cloning of ACP33 as a novel intracellular ligand of CD4.

CD4 recruitment to T cell receptor (TCR)-peptide-major histocompatibility class II complexes is required for stabilization of low affinity antigen recognition by T lymphocytes. The cytoplasmic portion of CD4 is thought to amplify TCR-initiated signal transduction via its association with the protein tyrosine kinase p56(lck). Here we describe a novel functional determinant in the cytosolic tail of CD4 that inhibits TCR-induced T cell activation. Deletion of two conserved hydrophobic amino acids from the CD4 carboxyl terminus resulted in a pronounced enhancement of CD4-mediated T cell costimulation. This effect was observed in the presence or absence of p56(lck), implying involvement of alternative cytosolic ligands of CD4. A two-hybrid screen with the intracellular portion of CD4 identified a previously unknown 33-kDa protein, ACP33 (acidic cluster protein 33), as a novel intracellular binding partner of CD4. Since interaction with ACP33 is abolished by deletion of the hydrophobic CD4 C-terminal amino acids mediating repression of T cell activation, we propose that ACP33 modulates the stimulatory activity of CD4. Furthermore, we demonstrate that interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of ACP33. This suggests a previously unrecognized function for alpha/beta hydrolase fold domains as a peptide binding module mediating protein-protein interactions.

Pubmed ID: 11113139


  • Zeitlmann L
  • Sirim P
  • Kremmer E
  • Kolanus W


The Journal of biological chemistry

Publication Data

March 23, 2001

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Antigens, CD4
  • COS Cells
  • Carrier Proteins
  • Cell Line
  • Cloning, Molecular
  • Endosomes
  • Golgi Apparatus
  • Humans
  • Ligands
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Subcellular Fractions
  • T-Lymphocytes