RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis.
The Ral signaling pathway is critically involved in Ras-dependent oncogenesis. One of its key actors, RLIP/RalBP1, which participates in receptor endocytosis during interphase, is also involved in mitotic processes when endocytosis is switched off. During mitosis, RLIP76 is located on the duplicated centrosomes and is required for their proper separation and movement to the poles. We have looked for actors that associate with RLIP during mitosis. We show here that RLIP/RalBP1 interacts with an active p34cdc2.cyclinB1 (cdk1) enzyme and that this interaction is crucial for the mitotic phosphorylation of Epsin that, once phosphorylated, is no longer competent for endocytosis. We show also that this latter phosphorylation is dependent on Ral signaling. We propose that RLIP/RalBP1 is used as a platform by the mitotic cdk1 to facilitate the phosphorylation of Epsin, which makes Epsin incompetent for endocytosis during mitosis, when endocytosis is switched off.
Rossé
Carine
C
Institut Curie, INSERM U528, Paris, France.
L'Hoste
Sébastien
S
Offner
Nicolas
N
Picard
André
A
Camonis
Jacques
J
D018528:ATP-Binding Cassette Transporters; D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004705:Endocytosis / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology; D020690:GTPase-Activating Proteins; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007605:Juvenile Hormones / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins; D020725:ral GTP-Binding Proteins / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D033962:Adaptor Protein Complex 2; D033942:Adaptor Proteins, Vesicular Transport; C534699:CCNB1 protein, human; D002352:Carrier Proteins; C503698:CycB protein, Drosophila; D019926:Cyclin B; D056744:Cyclin B1; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D007605:Juvenile Hormones; D009479:Neuropeptides; C095637:RALBP1 protein, human; D033921:Vesicular Transport Proteins; C114154:epsin; C060606:numb protein, Drosophila; D016203:CDC2 Protein Kinase; D020725:ral GTP-Binding Proteins