TBCK influences cell proliferation, cell size and mTOR signaling pathway

PLoS One. 2013 Aug 19;8(8):e71349. doi: 10.1371/journal.pone.0071349. eCollection 2013.

Abstract

Mammalian target of rapamycin (mTOR) is a central regulator for both cell proliferation and cell growth; however, little is known about the regulation of mTOR expression at the transcriptional level. Here, we provide evidences that a conserved human protein TBCK (TBC1 domain containing kinase) is involved in the regulation of mTOR signaling pathway. Depletion of TBCK significantly inhibits cell proliferation, reduces cell size, and disrupts the organization of actin, but not microtubule. Knockdown of TBCK induces a significant decrease in the protein levels of components of mTOR complex (mTORC), and suppresses the activity of mTOR signaling, but not MAPK or PDK1/Akt pathway. Further results show that TBCK influences the expression of mTORC components at the transcriptional level. Thus, these data suggest that TBCK may play an important role in cell proliferation, cell growth and actin organization possibly by modulating mTOR pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Actins / ultrastructure
  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Size
  • Conserved Sequence
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Transcription, Genetic

Substances

  • Actins
  • Multiprotein Complexes
  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • MTOR protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • TBCK protein, human
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases

Grants and funding

This study was funded by grants from the Ministry of Science and Technology of China (2012CB945004, 2013CB945603 and 2011CBA01001), the Natural Scientific Foundation of China (31125017, 31190063, 31071221 and 30771107), Doctoral Fund of Ministry of Education of China (20110101110103), the Natural Scientific Foundation of Zhejiang Province, China (Z2100247 and Y2100106), the 111 Project (B13026), the Department of Science and Technology of Zhejiang Province (2009C03012-3 and 2009F80005) and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.