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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Base Sequence
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Carrier Proteins / biosynthesis
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Cloning, Molecular
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DNA-Binding Proteins / metabolism
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Female
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Humans
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Jurkat Cells
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Male
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Molecular Sequence Data
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Molecular Weight
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NFATC Transcription Factors
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Nuclear Proteins*
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Organ Specificity
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Phosphoproteins / biosynthesis
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism*
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Polymerase Chain Reaction
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Protein-Tyrosine Kinases / metabolism*
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RNA, Messenger / analysis
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Receptors, Antigen, T-Cell / metabolism*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes
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Transcription Factors / metabolism
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Transcriptional Activation
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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FYB1 protein, human
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NFATC Transcription Factors
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Nuclear Proteins
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Phosphoproteins
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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SLP-76 signal Transducing adaptor proteins
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Transcription Factors
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Protein-Tyrosine Kinases