Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells.
Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the ... TCR zeta-chain in Jurkat cells. We now report that Shb also associates with phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation. Nuclear factor for activation of T cells is a major target for Ras and calcium signaling pathways in T cells following TCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma1 and resulting in the activation of transcription of the interleukin-2 gene.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Substitution, Calcium, Cytoplasm, DNA-Binding Proteins, GRB2 Adaptor Protein, Gene Expression Regulation, Humans, Interleukin-2, Isoenzymes, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Mitogen-Activated Protein Kinases, NFATC Transcription Factors, Nuclear Proteins, Phospholipase C gamma, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, Receptors, Antigen, T-Cell, Recombinant Proteins, T-Lymphocytes, Transcription Factors, Transfection, Type C Phospholipases, src Homology Domains
Adaptor Proteins, Signal Transducing, Amino Acid Substitution, Calcium, Cytoplasm, DNA-Binding Proteins, GRB2 Adaptor Protein, Gene Expression Regulation, Humans, Interleukin-2, Isoenzymes, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Mitogen-Activated Protein Kinases, NFATC Transcription Factors, Nuclear Proteins, Phospholipase C gamma, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, Receptors, Antigen, T-Cell, Recombinant Proteins, T-Lymphocytes, Transcription Factors, Transfection, Type C Phospholipases, src Homology Domains
J. Biol. Chem.
Date: Sep. 24, 1999
PubMed ID: 10488157
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