Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture

  • Zhang X
  • Shu L
  • Hosoi H
 et al. 
  • 2


    Mendeley users who have this article in their library.
  • N/A


    Citations of this article.


Mammalian target of rapamycin (mTOR) controls initiation of translation through regulation of ribosomal p70S6 kinase (S6K1) and eukaryotic translation initiation factor-4E (eIF4E) binding protein (4E-BP). mTOR is considered to be located predominantly in cytosolic or membrane fractions and may shuttle between the cytoplasm and nucleus. In most previous studies a single cell line, E1A-immortalized human embryonic kidney cells (HEK293), has been used. Here we show that in human malignant cell lines, human fibroblasts, and murine myoblasts mTOR is predominantly nuclear. In contrast, mTOR is largely excluded from the nucleus in HEK293 cells. Hybrids between HEK293 and Rh30 rhabdomyosarcoma cells generated cells co-expressing markers unique to HEK293 (E1A) and Rh30 (MyoD). mTOR distribution was mainly nuclear with detectable levels in the cytoplasm. mTOR isolated from Rh30 nuclei phosphorylated recombinant GST-4E-BP1 (Thr-46) in vitro and thus has kinase activity. We next investigated the cellular distribution of mTOR substrates 4E-BP, S6K1, and eIF4E. 4E-BP was exclusively detected in cytoplasmic fractions in all cell lines. S6K1 was localized in the cytoplasm in colon carcinoma, HEK293 cells, and IMR90 fibroblasts. S6K1 was readily detected in all cellular fractions derived from rhabdomyosarcoma cells. eIF4E was detected in all fractions derived from rhabdomyosarcoma cells but was not detectable in nuclear fractions from colon carcinoma HEK293 or IMR90 cells.

Author-supplied keywords

  • Animals
  • Antibodies: Monoclonal
  • Cell Line
  • Cell Nucleus
  • Humans
  • Kidney
  • Mice
  • Protein Kinases
  • Recombinant Proteins
  • Rhabdomyosarcoma
  • Transfection
  • Tumor Cells: Cultured

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in


  • Xiongwen Zhang

  • Lili Shu

  • Hajime Hosoi

  • K Gopal Murti

  • Peter J Houghton

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free