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

doi:10.2741/332

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 journal › Article › peer-review

88 Citations (Scopus)

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 language	English
Pages (from-to)	1289-1299
Number of pages	11
Journal	Frontiers in Bioscience-Elite
Volume	E3
Issue number	4
DOIs	https://doi.org/10.2741/332
Publication status	Published - 1 Jun 2011

Keywords

Amino acid transporter
SLC38A2 protein
Cell division
Cell proliferation
Human
Metabolism
Polyacrylamide gel electrophoresis
Signal transduction
Tumor cell line
Western blotting

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10.2741/332

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title = "SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation?",

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 = "Amino acid transporter, SLC38A2 protein, Cell division, Cell proliferation, Human, Metabolism, Polyacrylamide gel electrophoresis, Signal transduction, Tumor cell line, Western blotting",

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AU - Aledo, Juan Carlos

AU - Cwiklinski, Emma

AU - Hyde, Russell

AU - Taylor, Peter M.

AU - Hundal, Harinder S.

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AB - 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.

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KW - Cell proliferation

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KW - Signal transduction

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KW - Western blotting

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

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Keywords

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