Abstract
Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Blotting, Western
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Brain / embryology
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Brain / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Line
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Cell Membrane / metabolism
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Cell Membrane / ultrastructure
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Ephrin-B1
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Gene Deletion
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In Situ Hybridization
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism
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Neurons / ultrastructure
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Organ Specificity
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Phosphoamino Acids / metabolism
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Precipitin Tests
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Protein Serine-Threonine Kinases / metabolism
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Rats
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Ephrin-B1
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Grip1 protein, mouse
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Grip1 protein, rat
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Grip2 protein, mouse
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Grip2 protein, rat
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Nerve Tissue Proteins
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Phosphoamino Acids
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Protein Serine-Threonine Kinases
Associated data
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GENBANK/AF072509
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GENBANK/AJ133439