Vav3 is regulated during the cell cycle and effects cell division.
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.
Fujikawa
Keiko
K
Department of Neural Function, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Inoue
Yoshiro
Y
Sakai
Masaharu
M
Koyama
Yoshikazu
Y
Nishi
Shinzo
S
Funada
Ryo
R
Alt
Frederick W
FW
Swat
Wojciech
W
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
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