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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
by
Sinclair, Linda V
, Rolf, Julia
, Shi, Yun-Bo
, Cantrell, Doreen A
, Emslie, Elizabeth
, Taylor, Peter M
in
631/250/1619/554
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/2152/1566/2493
/ 631/250/516
/ 631/80/313
/ Amino acids
/ Amino Acids, Neutral - metabolism
/ Animals
/ Biomedicine
/ Cell differentiation
/ Cell Differentiation - genetics
/ Cell Proliferation
/ Cellular signal transduction
/ Cytotoxicity, Immunologic
/ Genetic aspects
/ Immune response
/ Immunology
/ Infectious Diseases
/ Interferon-gamma - metabolism
/ Interleukin-2 - metabolism
/ Large Neutral Amino Acid-Transporter 1 - genetics
/ Large Neutral Amino Acid-Transporter 1 - metabolism
/ Lymphocytes
/ Mice
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Nutrient uptake
/ Pathogens
/ Physiological aspects
/ Protein Transport
/ Receptors, Antigen, T-Cell, alpha-beta - metabolism
/ T cells
/ T-Lymphocytes, Cytotoxic - immunology
/ Up-Regulation
2013
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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
by
Sinclair, Linda V
, Rolf, Julia
, Shi, Yun-Bo
, Cantrell, Doreen A
, Emslie, Elizabeth
, Taylor, Peter M
in
631/250/1619/554
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/2152/1566/2493
/ 631/250/516
/ 631/80/313
/ Amino acids
/ Amino Acids, Neutral - metabolism
/ Animals
/ Biomedicine
/ Cell differentiation
/ Cell Differentiation - genetics
/ Cell Proliferation
/ Cellular signal transduction
/ Cytotoxicity, Immunologic
/ Genetic aspects
/ Immune response
/ Immunology
/ Infectious Diseases
/ Interferon-gamma - metabolism
/ Interleukin-2 - metabolism
/ Large Neutral Amino Acid-Transporter 1 - genetics
/ Large Neutral Amino Acid-Transporter 1 - metabolism
/ Lymphocytes
/ Mice
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Nutrient uptake
/ Pathogens
/ Physiological aspects
/ Protein Transport
/ Receptors, Antigen, T-Cell, alpha-beta - metabolism
/ T cells
/ T-Lymphocytes, Cytotoxic - immunology
/ Up-Regulation
2013
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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
by
Sinclair, Linda V
, Rolf, Julia
, Shi, Yun-Bo
, Cantrell, Doreen A
, Emslie, Elizabeth
, Taylor, Peter M
in
631/250/1619/554
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/2152/1566/2493
/ 631/250/516
/ 631/80/313
/ Amino acids
/ Amino Acids, Neutral - metabolism
/ Animals
/ Biomedicine
/ Cell differentiation
/ Cell Differentiation - genetics
/ Cell Proliferation
/ Cellular signal transduction
/ Cytotoxicity, Immunologic
/ Genetic aspects
/ Immune response
/ Immunology
/ Infectious Diseases
/ Interferon-gamma - metabolism
/ Interleukin-2 - metabolism
/ Large Neutral Amino Acid-Transporter 1 - genetics
/ Large Neutral Amino Acid-Transporter 1 - metabolism
/ Lymphocytes
/ Mice
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Nutrient uptake
/ Pathogens
/ Physiological aspects
/ Protein Transport
/ Receptors, Antigen, T-Cell, alpha-beta - metabolism
/ T cells
/ T-Lymphocytes, Cytotoxic - immunology
/ Up-Regulation
2013
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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
Journal Article
Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
2013
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Overview
T cell activation triggers proliferation and effector-cell differentiation. Cantrell and colleagues show that TCR signaling induces upregulation of amino-acid transporters necessary for metabolic reprogramming via the kinase complex mTORC1 and transcription factor c-Myc.
T lymphocytes must regulate nutrient uptake to meet the metabolic demands of an immune response. Here we show that the intracellular supply of large neutral amino acids (LNAAs) in T cells was regulated by pathogens and the T cell antigen receptor (TCR). T cells responded to antigen by upregulating expression of many amino-acid transporters, but a single System L ('leucine-preferring system') transporter, Slc7a5, mediated uptake of LNAAs in activated T cells. Slc7a5-null T cells were unable to metabolically reprogram in response to antigen and did not undergo clonal expansion or effector differentiation. The metabolic catastrophe caused by loss of Slc7a5 reflected the requirement for sustained uptake of the LNAA leucine for activation of the serine-threonine kinase complex mTORC1 and for expression of the transcription factor c-Myc. Control of expression of the System L transporter by pathogens is thus a critical metabolic checkpoint for T cells.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Amino Acids, Neutral - metabolism
/ Animals
/ Cell Differentiation - genetics
/ Cellular signal transduction
/ Interferon-gamma - metabolism
/ Large Neutral Amino Acid-Transporter 1 - genetics
/ Large Neutral Amino Acid-Transporter 1 - metabolism
/ Mice
/ Receptors, Antigen, T-Cell, alpha-beta - metabolism
/ T cells
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