Abstract
The human IL-4 receptor contains a sequence (the 14R motif) centered on Y497 that, when phosphorylated, interacts with phosphotyrosine-binding (PTB) domain proteins. Here, we describe a PTB domain protein, FRIP, that is phosphorylated in response to cytokine stimulation. FRIP is related to the rasGAP-associated protein p62dok and is bound by the N-terminal SH2 domain of rasGAP. The frip gene maps to the hairless (hr) locus on mouse chromosome 14. hr/hr mice exhibit lymphadenopathy, and their lymph node T cells proliferate more vigorously to anti-CD3 with IL-4 or IL-2 stimulation than +/hr T cells. FRIP expression is significantly reduced in T cells from hr/hr mice. FRIP may negatively regulate proliferation by acting as an adapter molecule between rasGAP and receptor complexes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Line
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Cell Line, Transformed
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Cells, Cultured
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Chromosome Mapping
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DNA, Complementary
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DNA-Binding Proteins*
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Female
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GTPase-Activating Proteins
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Humans
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Interleukin-2 / physiology
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Interleukin-3 / physiology
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Interleukin-4 / physiology*
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Phosphoproteins / chemistry
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Phosphorylation
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Phosphotyrosine / metabolism
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Proteins / genetics
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Proteins / metabolism*
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RNA, Messenger
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RNA-Binding Proteins*
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Receptors, Interleukin-4 / genetics
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Receptors, Interleukin-4 / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Tissue Distribution
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Transcription Factors*
Substances
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DNA, Complementary
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DNA-Binding Proteins
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DOK1 protein, human
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Dok1 protein, mouse
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GAP-associated protein p62
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GTPase-Activating Proteins
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HR protein, human
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Interleukin-2
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Interleukin-3
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Phosphoproteins
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Proteins
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RNA, Messenger
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RNA-Binding Proteins
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Receptors, Interleukin-4
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Recombinant Fusion Proteins
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Transcription Factors
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hr protein, mouse
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Interleukin-4
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Phosphotyrosine