Abstract
Transmembrane adaptor proteins (TRAPs) are important organizers and regulators of immunoreceptor-mediated signaling. A bioinformatic search revealed several potential novel TRAPs, including a highly conserved protein, proline rich 7 (PRR7), previously described as a component of the PSD-95/N-methyl-d-aspartate receptor protein complex in postsynaptic densities (PSD) of rat neurons. Our data demonstrate that PRR7 is weakly expressed in other tissues but is readily up-regulated in activated human peripheral blood lymphocytes. Transient overexpression of PRR7 in Jurkat T cell line led to gradual apoptotic death dependent on the WW domain binding motif surrounding Tyr-166 in the intracellular part of PRR7. To circumvent the pro-apoptotic effect of PRR7, we generated Jurkat clones with inducible expression of PRR7 (J-iPRR7). In these cells acute induction of PRR7 expression had a dual effect. It resulted in up-regulation of the transcription factor c-Jun and the activation marker CD69 as well as enhanced production of IL-2 after phorbol 12-myristate 13-acetate (PMA) and ionomycin treatment. On the other hand, expression of PRR7 inhibited general tyrosine phosphorylation and calcium influx after T cell receptor cross-linking by antibodies. Moreover, we found PRR7 constitutively tyrosine-phosphorylated and associated with Src. Collectively, these data indicate that PRR7 is a potential regulator of signaling and apoptosis in activated T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / biosynthesis*
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Amino Acid Motifs
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Animals
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caco-2 Cells
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Carcinogens / pharmacology
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Gene Expression Regulation / physiology*
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HEK293 Cells
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Humans
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics
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Interleukin-2 / immunology
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Jurkat Cells
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Lectins, C-Type / biosynthesis
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Phosphorylation / drug effects
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Phosphorylation / physiology
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / immunology
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Proto-Oncogene Proteins c-jun / metabolism
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Rats
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Tetradecanoylphorbol Acetate / pharmacology
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U937 Cells
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Carcinogens
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IL2 protein, human
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Interleukin-2
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Ionophores
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Lectins, C-Type
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Proto-Oncogene Proteins c-jun
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Receptors, Antigen, T-Cell
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Ionomycin
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Tetradecanoylphorbol Acetate