IMR Press / FBE / Volume 3 / Issue 4 / DOI: 10.2741/E332

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation?
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1 Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom

*Author to whom correspondence should be addressed.

Academic Editor: Guoyao Wu

Front. Biosci. (Elite Ed) 2011, 3(4), 1289–1299; https://doi.org/10.2741/E332
Published: 1 June 2011
(This article belongs to the Special Issue Amino acids in nutrition, health, and disease)
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.

Keywords
p70S6K1
System A
Me-AIB
Leucine
BCAA
Protein Synthesis
MCF-7 cells
L6 Myotubes
Muscle
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