An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein

Nat Struct Mol Biol. 2010 Sep;17(9):1051-7. doi: 10.1038/nsmb.1868. Epub 2010 Aug 8.


The phosphorylation state and corresponding activity of the retinoblastoma tumor suppressor protein (Rb) are modulated by a balance of kinase and phosphatase activities. Here we characterize the association of Rb with the catalytic subunit of protein phosphatase 1 (PP1c). A crystal structure identifies an enzyme docking site in the Rb C-terminal domain that is required for efficient PP1c activity toward Rb. The phosphatase docking site overlaps with the known docking site for cyclin-dependent kinase (Cdk), and PP1 competition with Cdk-cyclins for Rb binding is sufficient to retain Rb activity and block cell-cycle advancement. These results provide the first detailed molecular insights into Rb activation and establish a novel mechanism for Rb regulation in which kinase and phosphatase compete for substrate docking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Line
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase 2 / chemistry*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Humans
  • Models, Molecular
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs*
  • Protein Phosphatase 1 / chemistry*
  • Protein Phosphatase 1 / metabolism
  • Retinoblastoma Protein / chemistry*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*


  • Retinoblastoma Protein
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Protein Phosphatase 1

Associated data

  • PDB/3N5U