title: PDZ-Reactive Peptide Activates Ephrin-B Reverse Signaling and Inhibits Neuronal Chemotaxis.
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.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Food Safety and Technology Research Centre, State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hung Hom, Kowloon, Hong Kong SAR, China.
authors.forename: Tsz Tsun
authors.initials: TT
authors.lastname: Ng
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Food Safety and Technology Research Centre, State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hung Hom, Kowloon, Hong Kong SAR, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Yao
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University , Shenzhen, 518055, China.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects*; D002522:Chlorocebus aethiops; D015195:Drug Design; D036387:Ephrin-B1 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D036387:Ephrin-B1; C484572:LDB2 protein, human; D060588:LIM Domain Proteins; D010455:Peptides; D014157:Transcription Factors