title: Lipid phosphatases identified by screening a mouse phosphatase shRNA library regulate T-cell differentiation and protein kinase B AKT signaling.
abstract: Screening a complete mouse phosphatase lentiviral shRNA library using high-throughput sequencing revealed several phosphatases that regulate CD4 T-cell differentiation. We concentrated on two lipid phosphatases, the myotubularin-related protein (MTMR)9 and -7. Silencing MTMR9 by shRNA or siRNA resulted in enhanced T-helper (Th)1 differentiation and increased Th1 protein kinase B (PKB)/AKT phosphorylation while silencing MTMR7 caused increased Th2 and Th17 differentiation and increased AKT phosphorylation in these cells. Irradiated mice reconstituted with MTMR9 shRNA-transduced bone marrow cells had an elevated proportion of T-box transcription factor T-bet expressors among their CD4 T cells. After adoptive transfer of naïve cells from such reconstituted mice, immunization resulted in a greater proportion of T-box transcription factor T-bet-expressing cells. Thus, myotubularin-related proteins have a role in controlling in vitro and in vivo Th-cell differentiation, possibly through regulation of phosphatidylinositol [3,4,5]-trisphosphate activity.
authors: Cytokine Biology Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Liying
authors: L
authors: Guo
authors: Craig
authors: C
authors: Martens
authors: Daniel
authors: D
authors: Bruno
authors: Stephen F
authors: SF
authors: Porcella
authors: Hidehiro
authors: H
authors: Yamane
authors: Stephane M
authors: SM
authors: Caucheteux
authors: Jinfang
authors: J
authors: Zhu
authors: William E
authors: WE
authors: Paul
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D015723:Gene Library; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C478104:Mtmr7 protein, mouse; C478105:Mtmr9 protein, mouse; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
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