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: J M Sterner, Y Tao, S B Kennett, H G Kim, J M Horowitz
• Journal: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research (Cell Growth Differ) Vol. 7 Issue 1 Pg. 53-64 (Jan 1996) ISSN: 1044-9523 [Print] United States
• PMID: 8788033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Growth Inhibitors
• Nuclear Proteins
• Phosphoproteins
• Proteins
• Proto-Oncogene Proteins c-myc
• RBL1 protein, human
• RBL2 protein, human
• Retinoblastoma Protein
• Retinoblastoma-Like Protein p107
• Retinoblastoma-Like Protein p130
• Cyclin-Dependent Kinases
• Maturation-Promoting Factor

Topics

• Base Sequence
• Cyclin-Dependent Kinases (metabolism)
• Growth Inhibitors (metabolism)
• Humans
• Leukemia, Myeloid
• Maturation-Promoting Factor (genetics, metabolism)
• Mitosis (physiology)
• Molecular Sequence Data
• Mutation (physiology)
• Nuclear Proteins (metabolism, ultrastructure)
• Phosphoproteins (metabolism, ultrastructure)
• Phosphorylation
• Proteins
• Proto-Oncogene Proteins c-myc (genetics, metabolism, ultrastructure)
• Retinoblastoma (genetics, metabolism)
• Retinoblastoma Protein (metabolism, ultrastructure)
• Retinoblastoma-Like Protein p107
• Retinoblastoma-Like Protein p130
• Sequence Homology, Amino Acid
• Transcription, Genetic (physiology)
• Tumor Cells, Cultured (cytology, enzymology)