Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2.
Entry of a cell into mitosis induces a series of structural and functional changes including arrest of intracellular transport. Knowledge of how the mitotic cycle is driven progressed substantially with the identification of the p34cdc2 protein kinase as a subunit of maturation-promoting factor, the universal regulating component of the mitotic cycle. Activation of the kinase at the onset of mitosis is thought to trigger the important mitotic events by phosphorylating key proteins. Small guanine nucleotide-binding proteins have been implicated in regulating transport pathways. For instance, two small Ras-related GTP-binding proteins, Sec4p and Ypt1p, control distinct stages of the secretory pathway in budding yeast. The GTP-binding proteins of the Rab family in rats and humans display strong homologies with Sec4p and Ypt1p, and might therefore also be involved in regulating intracellular transport. Indeed, distinct Rab proteins are located in the exocytotic and endocytotic compartments. Interruption of vesicular transport during mitosis might involve modification of these proteins. We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of Rab1Ap and Rab4p. By contrast, Rab2p and Rab6p are not phosphorylated. We also show that the distribution of Rab1Ap and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells. This may provide a clue to the mechanism by which phosphorylation could affect membrane traffic during mitosis.
Bailly
E
E
Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France.
McCaffrey
M
M
Touchot
N
N
Zahraoui
A
A
Goud
B
B
Bornens
M
M
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007399:Interphase; D008938:Mitosis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D012689:Sequence Homology, Nucleic Acid
D016203:CDC2 Protein Kinase; D019204:GTP-Binding Proteins