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Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner

Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner
Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner
Amino acids exert modulatory effects on proteins involved in control of mRNA translation in animal cells through the target of rapamycin (TOR) signaling pathway. Here we use oocytes of Xenopus laevis to investigate mechanisms by which amino acids are "sensed" in animal cells. Small (~48%) but physiologically relevant increases in intracellular but not extracellular total amino acid concentration (or Leu or Trp but not Ala, Glu, or Gln alone) resulted in increased phosphorylation of p70S6K and its substrate ribosomal protein S6. This response was inhibited by rapamycin, demonstrating that the effects require the TOR pathway. Alcohols of active amino acids substituted for amino acids with lower efficiency. Oocytes were refractory to changes in external amino acid concentration unless surface permeability of the cell to amino acids was increased by overexpression of the System L amino acid transporter. Amino acid-induced, rapamycin-sensitive activation of p70S6K was conferred when System L-expressing oocytes were incubated in extracellular amino acids, supporting intracellular localization of the putative amino acid sensor. In contrast to lower eukaryotes such as yeast, which possess an extracellular amino acid sensor, our findings provide the first direct evidence for an intracellular location for the putative amino acid sensor in animal cells that signals increased amino acid availability to TOR/p70S6K.
0021-9258
9952-9957
Christie, G.R.
21148ec2-8f8c-42e9-9f78-572d137bcc82
Hajduch, E.
6364963e-17eb-4986-96cd-1ee5c102631b
Hundal, H.S.
ef0a6638-5caf-4bbe-8a49-b845ff024713
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Taylor, P.M.
329d2e7a-e045-4ee6-9a73-6c423b5c0420
Christie, G.R.
21148ec2-8f8c-42e9-9f78-572d137bcc82
Hajduch, E.
6364963e-17eb-4986-96cd-1ee5c102631b
Hundal, H.S.
ef0a6638-5caf-4bbe-8a49-b845ff024713
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Taylor, P.M.
329d2e7a-e045-4ee6-9a73-6c423b5c0420

Christie, G.R., Hajduch, E., Hundal, H.S., Proud, C.G. and Taylor, P.M. (2002) Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner. The Journal of Biological Chemistry, 277, 9952-9957. (doi:10.1074/jbc.M107694200).

Record type: Article

Abstract

Amino acids exert modulatory effects on proteins involved in control of mRNA translation in animal cells through the target of rapamycin (TOR) signaling pathway. Here we use oocytes of Xenopus laevis to investigate mechanisms by which amino acids are "sensed" in animal cells. Small (~48%) but physiologically relevant increases in intracellular but not extracellular total amino acid concentration (or Leu or Trp but not Ala, Glu, or Gln alone) resulted in increased phosphorylation of p70S6K and its substrate ribosomal protein S6. This response was inhibited by rapamycin, demonstrating that the effects require the TOR pathway. Alcohols of active amino acids substituted for amino acids with lower efficiency. Oocytes were refractory to changes in external amino acid concentration unless surface permeability of the cell to amino acids was increased by overexpression of the System L amino acid transporter. Amino acid-induced, rapamycin-sensitive activation of p70S6K was conferred when System L-expressing oocytes were incubated in extracellular amino acids, supporting intracellular localization of the putative amino acid sensor. In contrast to lower eukaryotes such as yeast, which possess an extracellular amino acid sensor, our findings provide the first direct evidence for an intracellular location for the putative amino acid sensor in animal cells that signals increased amino acid availability to TOR/p70S6K.

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Published date: 1 March 2002

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Local EPrints ID: 56501
URI: http://eprints.soton.ac.uk/id/eprint/56501
ISSN: 0021-9258
PURE UUID: b269c304-36d7-448d-ae8e-5c58b861e818

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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 11:02

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Contributors

Author: G.R. Christie
Author: E. Hajduch
Author: H.S. Hundal
Author: C.G. Proud
Author: P.M. Taylor

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