title: UNC119a bridges the transmission of Fyn signals to Rab11, leading to the completion of cytokinesis.
abstract: Src family kinases (SFKs) regulate the completion of cytokinesis through signal transduction pathways that lead to the Rab11-dependent phosphorylation of ERK and its localization to the midbody of cytokinetic cells. We find that UNC119a, a known activator of SFKs, plays essential roles in this signaling pathway. UNC119a localizes to the centrosome in interphase cells and begins to translocate from the spindle pole to the spindle midzone after the onset of mitosis; it then localizes to the intercellular bridge in telophase cells and to the midbody in cytokinetic cells. We show that the midbody localization of UNC119a is dependent on Rab11, and that knocking down UNC119a inhibits the Rab11-dependent phosphorylation and midbody localization of ERK and cytokinesis. Moreover, we demonstrate that UNC119a interacts with a Src family kinase, Fyn and is required for the activation of this kinase. These results suggest that UNC119a plays a key role in the Fyn signal transduction pathway, which regulates the completion of cytokinesis via Rab11.
authors.affiliation: Department of Systems Biology, Yonsei University, Seoul, Korea.
authors.forename: YuKyung
authors.initials: Y
authors.lastname: Lee
authors.forename: Sunglan
authors.initials: S
authors.lastname: Chung
authors.forename: In Keol
authors.initials: IK
authors.lastname: Baek
authors.forename: Tae H
authors.initials: TH
authors.lastname: Lee
authors.forename: Soon-Yong
authors.initials: SY
authors.lastname: Paik
authors.forename: JooHun
authors.initials: J
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D048749:Cytokinesis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D009841:Oligonucleotides / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009841:Oligonucleotides; D051076:Proto-Oncogene Proteins c-fyn; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C098032:UNC119 protein, human; C494957:FYN protein, human
keywords: Fyn kinase; Rab11; SFKs signaling; UNC119; cytokinesis; cytokinesis failure
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