Abstract
Intracellular reactions on nonenzymatic proteins that activate cellular signals are rarely found. We report one example here that a designed peptide derivative undergoes a nucleophilic reaction specifically with a cytosolic PDZ protein inside cells. This reaction led to the activation of ephrin-B reverse signaling, which subsequently inhibited SDF-1 induced neuronal chemotaxis of human neuroblastoma cells and mouse cerebellar granule neurons. Our work provides direct evidence that PDZ-RGS3 bridges ephrin-B reverse signaling and SDF-1 induced G protein signaling for the first time.
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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COS Cells
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Cell Line, Tumor
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Chemotaxis / drug effects*
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Chlorocebus aethiops
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Drug Design*
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Ephrin-B1 / metabolism*
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HEK293 Cells
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Humans
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LIM Domain Proteins / chemistry
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Mice
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Mice, Inbred C57BL
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Models, Molecular
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Molecular Sequence Data
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Neurons / drug effects*
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Peptides / chemical synthesis
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Peptides / genetics
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Peptides / pharmacology*
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Protein Structure, Tertiary
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Signal Transduction / drug effects*
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Transcription Factors / chemistry
Substances
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Ephrin-B1
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LDB2 protein, human
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LIM Domain Proteins
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Peptides
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Transcription Factors