title: PRR7 is a transmembrane adaptor protein expressed in activated T cells involved in regulation of T cell receptor signaling and apoptosis.
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.
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors: Matous
authors: M
authors: Hrdinka
authors: Peter
authors: P
authors: Dráber
authors: Ondrej
authors: O
authors: Stepánek
authors: Tereza
authors: T
authors: Ormsby
authors: Pavel
authors: P
authors: Otáhal
authors: Pavla
authors: P
authors: Angelisová
authors: Tomás
authors: T
authors: Brdicka
authors: Jan
authors: J
authors: Paces
authors: Václav
authors: V
authors: Horejsí
authors: Karel
authors: K
authors: Drbal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018938:Caco-2 Cells; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells; D000099192:CD69 Antigens
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002273:Carcinogens; D007376:Interleukin-2; D015759:Ionomycin; D007476:Ionophores; D037181:Lectins, C-Type; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C508594:IL2 protein, human