title: The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression.
abstract: Centralspindlin, which is composed of MgcRacGAP and MKLP1, is essential for central spindle formation and cytokinetic furrow ingression. MgcRacGAP utilizes its GAP domain to inactivate Rac1 and induce furrow ingression in mammalian cells. In this report, we present a novel regulatory mechanism for furrowing that is mediated by the phosphorylation of SHC SH2-domain binding protein 1 (SHCBP1), a binding partner of centralspindlin, by Aurora B (AurB). AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing. An in vitro GAP assay demonstrated that SHCBP1 can suppress the MgcRacGAP-mediated inactivation of Rac1. In addition, the inhibition of Rac1 activity rescued the furrowing defect induced by S634A-SHCBP1 expression. Thus, AurB phosphorylates SHCBP1 to prevent the premature localization of SHCBP1 to the central spindle and ensures that MgcRacGAP inactivates Rac1 to promote the ingression of the cytokinetic furrow.
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D000595:Amino Acid Sequence; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C000599466:SHCBP1 protein, human; D055765:Shc Signaling Adaptor Proteins; D064107:Aurora Kinase B
keywords: Aurora B; Central spindle; Centralspindlin; Cytokinesis; SHCBP1