Lipid phosphatases identified by screening a mouse phosphatase shRNA library regulate T-cell differentiation and protein kinase B AKT signaling

Proc Natl Acad Sci U S A. 2013 May 14;110(20):E1849-56. doi: 10.1073/pnas.1305070110. Epub 2013 Apr 29.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Profiling
  • Gene Library
  • Gene Silencing
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • PTEN Phosphohydrolase / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / metabolism
  • T-Lymphocytes / cytology*
  • Th17 Cells / cytology
  • Th2 Cells / cytology


  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt
  • Mtmr7 protein, mouse
  • Mtmr9 protein, mouse
  • Protein Tyrosine Phosphatases, Non-Receptor
  • PTEN Phosphohydrolase
  • Pten protein, mouse