title: High molecular weight protein phosphatase type 1 dephosphorylates the retinoblastoma protein.
abstract: pRb controls cell proliferation by restricting inappropriate entry of cells into the cell division cycle. As dephosphorylation of pRb during mitotic exit activates its growth suppressive function, identification of the protein phosphatase that dephosphorylates pRb, and characterization of the mechanism of its regulation, are essential to elucidating the mechanisms of cell growth control. By fractionating mitotic CV-1P cell extracts, we identify the protein phosphatase which dephosphorylates pRb as a type 1 serine/threonine phosphoprotein phosphatase (PP1). Molecular sizing analyses indicate that the catalytic enzyme (PP1c) is present in a high molecular weight complex, with a predicted molecular mass of 166 kDa. PP1-interacting proteins in the mitotic cell extracts are identified. Two PP1-interacting proteins (41 and 110 kDa) are shown to form distinct complexes with PP1c from fractions of separated mitotic cell extracts containing phosphorylase phosphatase activity. However, only the 110-kDa PP1-interacting protein is present in fractions containing pRb-directed phosphatase activity, identifying this protein as a putative activator of PP1 function toward pRb during mitosis.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Nelson
authors.forename: N A
authors.initials: NA
authors.lastname: Krucher
authors.forename: J W
authors.initials: JW
authors.lastname: Ludlow
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002457:Cell Extracts; D002460:Cell Line; D002850:Chromatography, Gel; D000882:Haplorhini; D008938:Mitosis; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D054645:Protein Phosphatase 1; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D002457:Cell Extracts; D016160:Retinoblastoma Protein; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1