title: Vav3 is regulated during the cell cycle and effects cell division.
abstract: Vav3 is a member of the family of guanine nucleotide exchange factors implicated in the regulation of Rho GTPases. Although the exact in vivo function of Vav3 is unknown, evidence from several studies indicates a role distinct from Vav2 or Vav1. Here we report that the expression of Vav3 is regulated during the cell cycle. Strikingly, Vav3 was transiently up-regulated in HeLa cells during mitosis, whereas enforced expression of Vav3 perturbed cytokinesis and led to the appearance of multinucleated cells. These effects of Vav3 were RhoA-dependent, required phosphorylation of the regulatory tyrosine 173, but were not enhanced by N-terminal truncations. Thus, this report establishes that expression of Vav3 is strictly regulated in a cell cycle-dependent manner and implicates Vav3 in the control of cytokinesis.
authors.affiliation: Department of Neural Function, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Koyama
authors.forename: Shinzo
authors.initials: S
authors.lastname: Nishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Funada
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Swat
mesh_terms: D000469:Alkaline Phosphatase; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger / Q000032:analysis; D013329:Structure-Activity Relationship
chemical_list: D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger; C496621:VAV3 protein, human; D018844:Cyclin-Dependent Kinases; D000469:Alkaline Phosphatase