PDZ-Reactive Peptide Activates Ephrin-B Reverse Signaling and Inhibits Neuronal Chemotaxis

ACS Chem Biol. 2016 Jan 15;11(1):149-58. doi: 10.1021/acschembio.5b00889. Epub 2015 Nov 9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Chemotaxis / drug effects*
  • Chlorocebus aethiops
  • Drug Design*
  • Ephrin-B1 / metabolism*
  • HEK293 Cells
  • Humans
  • LIM Domain Proteins / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Molecular Sequence Data
  • Neurons / drug effects*
  • Peptides / chemical synthesis
  • Peptides / genetics
  • Peptides / pharmacology*
  • Protein Structure, Tertiary
  • Signal Transduction / drug effects*
  • Transcription Factors / chemistry

Substances

  • Ephrin-B1
  • LDB2 protein, human
  • LIM Domain Proteins
  • Peptides
  • Transcription Factors