Abstract
Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain. A mutant T cell line was isolated that lacked expression of SLP-76 (SH2 domain-containing leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), as well as Ras pathway activation. TCR-inducible gene expression was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.
Publication types
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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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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism
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Cell Line
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Gene Expression Regulation
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Humans
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Inositol Phosphates / metabolism
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Interleukin-2 / genetics
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Isoenzymes / metabolism*
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Jurkat Cells
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Membrane Proteins*
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Mitogen-Activated Protein Kinase 1
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NFATC Transcription Factors
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Nuclear Proteins*
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Phospholipase C gamma
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Phosphoproteins / metabolism
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Phosphoproteins / physiology*
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction
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T-Lymphocytes / enzymology
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T-Lymphocytes / metabolism*
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Transcription Factors / metabolism
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Transcriptional Activation
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Transfection
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Type C Phospholipases / metabolism*
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ras Proteins / metabolism
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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Inositol Phosphates
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Interleukin-2
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Isoenzymes
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LAT protein, human
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Membrane Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Phosphoproteins
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Receptors, Antigen, T-Cell
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SLP-76 signal Transducing adaptor proteins
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Transcription Factors
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Phosphotyrosine
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Protein-Tyrosine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Type C Phospholipases
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Phospholipase C gamma
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ras Proteins
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Calcium