Abstract
Sos proteins are ubiquitously expressed activators of Ras. Lymphoid cells also express RasGRP1, another Ras activator. Sos and RasGRP1 are thought to cooperatively control full Ras activation upon T-cell receptor triggering. Using RNA interference, we evaluated whether this mechanism operates in primary human T cells. We found that T-cell antigen receptor (TCR)-mediated Erk activation requires RasGRP1, but not Grb2/Sos. Conversely, Grb2/Sos—but not RasGRP1—are required for IL2-mediated Erk activation. Thus, RasGRP1 and Grb2/Sos are insulators of signals that lead to Ras activation induced by different stimuli, rather than cooperating downstream of the TCR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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Enzyme Activation / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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GRB2 Adaptor Protein / metabolism*
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Gene Knockdown Techniques
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Guanine Nucleotide Exchange Factors / metabolism
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Humans
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Interleukin-2 / pharmacology
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Lymphocyte Activation / drug effects
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Phosphorylation / drug effects
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RNA, Small Interfering / metabolism
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Interleukin-2 / metabolism
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Son of Sevenless Protein, Drosophila / metabolism*
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology
Substances
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DNA-Binding Proteins
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GRB2 Adaptor Protein
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GRB2 protein, human
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Guanine Nucleotide Exchange Factors
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Interleukin-2
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RASGRP1 protein, human
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RNA, Small Interfering
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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Son of Sevenless Protein, Drosophila
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Extracellular Signal-Regulated MAP Kinases