title: The amino terminus of the retinoblastoma (Rb) protein associates with a cyclin-dependent kinase-like kinase via Rb amino acids required for growth suppression.
abstract: We have shown previously that a novel cell cycle-regulated histone H1 kinase activity, retinoblastoma kinase (RbK), associates with and phosphorylates the amino terminus of the Rb protein in G2-M. We have shown also that the amino terminus of p107, a Rb-related protein, does not associate with a similar kinase in vitro or in vivo. Here, we report that a RbK-like kinase associates with the amino terminus of p130, another Rb-related protein, only marginally. Moreover, the association of RbK with Rb in vitro is shown to require a discrete portion of the Rb amino terminus, amino acids 89-202. This region has been shown previously to be subject to inactivating mutations in retinoblastoma and to be required for Rb-mediated growth suppression in vitro. Taken together, these data indicate that the formation of Rb-RbK complexes may play an important role in Rb-mediated growth suppression. We have mapped two in vitro sites of Rb phosphorylation by RbK to sites that are phosphorylated in vivo and are targets of cyclin-dependent kinase phosphorylation in vitro. As such, at least some sites of RbK phosphorylation overlap with those of other proline-directed serine and threonine kinases. Consistent with this latter observation, we report that the trans-activation domain of c-myc is phosphorylated specifically by RbK in vitro at a site (serine 62) that is phosphorylated in vivo during G2-M, cell-cycle phases in which RbK activity is maximal.
authors.affiliation: Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Sterner
authors.forename: Y
authors.initials: Y
authors.lastname: Tao
authors.forename: S B
authors.initials: SB
authors.lastname: Kennett
authors.forename: H G
authors.initials: HG
authors.lastname: Kim
authors.forename: J M
authors.initials: JM
authors.lastname: Horowitz
mesh_terms: D001483:Base Sequence; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid; D016200:Maturation-Promoting Factor / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism* / Q000648:ultrastructure; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology
chemical_list: D006131:Growth Inhibitors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D018844:Cyclin-Dependent Kinases; D016200:Maturation-Promoting Factor