Abstract
Sos-1 and Sos-2 are ubiquitously expressed Ras-guanine exchange factors involved in Erk-MAP kinase pathway activation. Using mice lacking genes encoding Sos-1 and Sos-2, we evaluated the role of these proteins in peripheral T-cell signaling and function. Our results confirmed that TCR-mediated Erk activation in peripheral CD4(+) T cells does not depend on Sos-1 and Sos-2, although IL-2-mediated Erk activation does. Unexpectedly, however, we show an increase in AKT phosphorylation in Sos-1/2dKO CD4(+) T cells upon TCR and IL-2 stimulation. Activation of AKT was likely a consequence of increased recruitment of PI3K to Grb2 upon TCR and/or IL-2 stimulation in Sos-1/2dKO CD4(+) T cells. The increased activity of the PI3K/AKT pathway led to downregulation of the surface receptor CD62L in Sos-1/2dKO T cells and a subsequent impairment in T-cell migration.
Keywords:
CD62L; Erk; Grb2; PI3K/AKT; Signaling; Sos; T cell.
Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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Cell Movement / genetics
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Cell Movement / immunology*
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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GRB2 Adaptor Protein / genetics
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GRB2 Adaptor Protein / immunology
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Interleukin-2 / genetics
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Interleukin-2 / immunology
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L-Selectin / genetics
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L-Selectin / immunology
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Mice
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Mice, Knockout
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / immunology*
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Phosphorylation / genetics
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Phosphorylation / immunology
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / immunology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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SOS1 Protein / genetics
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SOS1 Protein / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Son of Sevenless Proteins / genetics
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Son of Sevenless Proteins / immunology*
Substances
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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Interleukin-2
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Receptors, Antigen, T-Cell
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SOS1 Protein
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Son of Sevenless Proteins
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Sos2 protein, mouse
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L-Selectin
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt