title: Effects of protein tyrosine phosphatase-PEST are reversed by Akt in T cells.
abstract: T cell activation is regulated by a balance between phosphorylation and dephosphorylation that is under the control of kinases and phosphatases. Here, we examined the role of a non-receptor-type protein tyrosine phosphatase, PTP-PEST, using retrovirus-mediated gene transduction into murine T cells. Based on observations of vector markers (GFP or Thy1.1), exogenous PTP-PEST-positive CD4(+) T cells appeared within 2 days after gene transduction; the percentage of PTP-PEST-positive cells tended to decrease during a resting period in the presence of IL-2 over the next 2 days. These vector markers also showed much lower expression intensities, compared with control cells, suggesting a correlation between the percent reduction and the low marker expression intensity. A catalytically inactive PTP-PEST mutant also showed the same tendency, and stepwise deletion mutants gradually lost their ability to induce the above phenomenon. On the other hand, these PTP-PEST-transduced cells did not have an apoptotic phenotype. No difference in the total cell numbers was found in the wells of a culture plate containing VEC- and PTP-PEST-transduced T cells. Moreover, serine/threonine kinase Akt, but not the anti-apoptotic molecules Bcl-2 and Bcl-XL, reversed the phenotype induced by PTP-PEST. We discuss the novel mechanism by which Akt interferes with PTP-PEST.
authors.affiliation: Host Defense for Animals, Nippon Veterinary and Life Science University, 1-7-1 Kyonan, Musashino, Tokyo, 180-8602 Japan; Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada, Shinjuku, Tokyo, 162-8666 Japan. Electronic address: arimura2013@nvlu.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Arimura
authors.affiliation: Anatomy and Developmental Biology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada, Shinjuku, Tokyo, 162-8666 Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Host Defense for Animals, Nippon Veterinary and Life Science University, 1-7-1 Kyonan, Musashino, Tokyo, 180-8602 Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Koyanagi
authors.affiliation: Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada, Shinjuku, Tokyo, 162-8666 Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yagi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases
keywords: Akt; Cell death; Growth factor signaling; PTP-PEST; Protein Tyrosine Phosphatase (PTP)