Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity

J Immunol. 1996 Nov 1;157(9):3769-73.


SLP-76 (SH2 domain leukocyte protein of 76 kDa) is a recently identified substrate of the TCR-stimulated protein tyrosine kinases that functions in the signal transduction cascade linking the TCR with IL-2 gene expression. In this report, we demonstrate that engagement of the TCR results in tyrosine phosphorylation of SLP-76 in its amino-terminal acidic region. Two tyrosines (Y113 and Y128) fall within an identical five amino-acid motif and are shown to be phosphorylated upon TCR ligation. Although mutation of either Y113 and Y128 has a minimal effect on SLP-76 function, mutation of both residues decreases significantly the ability of SLP-76 to promote T cell activation. A third tyrosine within the amino-terminal region (Y145) appears to be the most important for optimal SLP-76 function, as altering it alone to phenylalanine has a potent impact on SLP-76 augmentation of NFAT promoter activity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Leukemic
  • Humans
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Neoplasm Proteins / physiology
  • Nuclear Proteins*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / pharmacology
  • Phosphorylation
  • Promoter Regions, Genetic*
  • Protein Processing, Post-Translational*
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / physiology*
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Tyrosine / physiology*


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • Neoplasm Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • Transcription Factors
  • Tyrosine
  • Protein-Tyrosine Kinases