Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases

J Biol Chem. 1997 May 2;272(18):11674-7. doi: 10.1074/jbc.272.18.11674.

Abstract

Previous work has demonstrated that SLP-76, a Grb2-associated tyrosine-phosphorylated protein, augments Interleukin-2 promoter activity when overexpressed in the Jurkat T cell line. This activity requires regions of SLP-76 that mediate protein-protein interactions with other molecules in T cells, suggesting that SLP-76-associated proteins also function to regulate signal transduction. Here we describe the molecular cloning of SLAP-130, a SLP-76-associated phosphoprotein of 130 kDa. We demonstrate that SLAP-130 is hematopoietic cell-specific and associates with the SH2 domain of SLP-76. Additionally, we show that SLAP-130 is a substrate of the T cell antigen receptor-induced protein tyrosine kinases. Interestingly, we find that in contrast to SLP-76, overexpression of SLAP-130 diminishes T cell antigen receptor-induced activation of the interleukin-2 promoter in Jurkat T cells and interferes with the augmentation of interleukin-2 promoter activity seen when SLP-76 is overexpressed in these cells. These data suggest that SLP-76 recruits a negative regulator, SLAP-130, as well as positive regulators of signal transduction in T cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Jurkat Cells
  • Male
  • Molecular Sequence Data
  • Molecular Weight
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Organ Specificity
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases / metabolism*
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • FYB1 protein, human
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • SLP-76 signal Transducing adaptor proteins
  • Transcription Factors
  • Protein-Tyrosine Kinases

Associated data

  • GENBANK/U93049