SNAT2 transceptor signalling via mTOR: A role in cell growth and proliferation?

Jorge Pinilla, Juan Carlos Aledo, Emma Cwiklinski, Russell Hyde, Peter M. Taylor, Harinder S. Hundal

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

We have investigated the effect of chronic competitive inhibition of SNAT2 (System A) amino acid (AA) transport, induced by incubation with a saturating dose of a non-metabolisable System A amino acid analogue (Me-AIB), on growth and proliferation of MCF-7 human breast cancer cells in complete culture medium. These cells express Na+- and pH-dependent SNAT2 AA transport and a saturating concentration of Me-AIB (10 mM) competitively inhibits (>90%) AA uptake via SNAT2. Incubation with Me-AIB for up to 5 days progressively reduced cell proliferation (∼2-fold) and depleted intracellular concentrations of not only SNAT2 AA substrates but of essential branched chain AAs (e.g. leucine). Surprisingly, total cellular protein was maintained and cells subjected to chronic Me-AIB incubation exhibited a detectable increase in cell size. Analysis of mTOR signalling revealed that, despite a substantial reduction in size of the intracellular AA pool, Me-AIB elevated mTOR-dependent p70S6K1 phosphorylation. Proteomic analysis of TAP-tag purified SNAT2 fusion proteins identified two novel SNAT2-interacting proteins that may potentially function in conjunction with the SNAT2 transceptor to regulate signalling pathways influencing protein turnover and cell growth.

Original languageEnglish
Pages (from-to)1289-1299
Number of pages11
JournalFrontiers in Bioscience - Elite
Volume3 E
Issue number4
StatePublished - Jan 6 2011

Keywords

  • BCAA
  • L6 myotubes
  • Leucine
  • MCF-7 cells
  • Me-AIB
  • Muscle
  • P70S6K1
  • Protein synthesis
  • System A

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