Abstract
The mammalian target of rapamycin (mTOR) kinase is a critical regulator of the differentiation of helper and regulatory CD4+ T cells, as well as memory CD8+ T cells. In this study, we investigated the role of the ERK signaling pathway in regulating mTOR activation in T cells. We showed that activation of ERK following TCR engagement is required for sustained mTOR complex 1 (mTORC1) activation. Absence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation. However, KSR1-deficient mice displayed normal regulatory CD4+ T cell development, as well as normal memory CD8+ T cell responses to LCMV and Listeria monocytogenes infection. These data indicate that despite its role in mTORC1 activation, KSR1 is not required in vivo for mTOR-dependent T cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / enzymology*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / physiology
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Cell Differentiation
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Cells, Cultured
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Immunologic Memory
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Listeria monocytogenes / immunology
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Listeriosis / immunology
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MAP Kinase Signaling System
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Mechanistic Target of Rapamycin Complex 1
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Multiprotein Complexes
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Protein Kinases / metabolism*
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Proteins / metabolism
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T-Lymphocytes, Regulatory / enzymology*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / physiology
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TOR Serine-Threonine Kinases / metabolism
Substances
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Multiprotein Complexes
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Proteins
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Protein Kinases
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KSR-1 protein kinase
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mTOR protein, mouse
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Mechanistic Target of Rapamycin Complex 1
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TOR Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase Kinases