Abstract
Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues. Grap(-/-) lymphocytes isolated from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2 production, and c-fos induction in response to mitogenic T-cell receptor (TCR) stimulation, compared to wild-type cells. Ectopic expression of Grap led to a suppression of Elk-1-directed transcription induced by the Ras/Erk pathway, without having effects on gene expression mediated by Jnk and p38 mitogen-activated protein kinases. Together, these data suggest that Grap, unlike Grb2, acts as a negative regulator of TCR-stimulated intracellular signaling by downregulating signal relay through the Ras/Erk pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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DNA-Binding Proteins*
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Enzyme Activation
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Gene Expression Regulation
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Genes, Reporter
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Interleukin-2 / metabolism*
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Lymphocyte Activation
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Lymphocytes / metabolism*
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction / physiology*
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Transcription Factors*
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ets-Domain Protein Elk-1
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ras Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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Elk1 protein, mouse
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Interleukin-2
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Mona protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-fos
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Receptors, Antigen, T-Cell
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Transcription Factors
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ets-Domain Protein Elk-1
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Mitogen-Activated Protein Kinases
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ras Proteins