PMID- 10506210
OWN - NLM
STAT- MEDLINE
DCOM- 19991109
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 41
DP  - 1999 Oct 8
TI  - Inhibitory phosphorylation of PP1alpha catalytic subunit during the G(1)/S
      transition.
PG  - 29470-5
AB  - We have shown earlier that, in cells expressing the retinoblastoma protein (pRB),
      a protein phosphatase (PP) 1alpha mutant (T320A) resistant to inhibitory
      phosphorylation by cyclin-dependent kinases (Cdks) causes G(1) arrest. In this
      study, we examined the cell cycle-dependent phosphorylation of PP1alpha in vivo
      using three different antibodies. PP1alpha was phosphorylated at Thr-320 during
      M-phase and again in late G(1)- through early S-phase. Inhibition of Cdk2 led to 
      a small increase in PP1 activity and also prevented PP1alpha phosphorylation. In 
      vitro, PP1alpha was a substrate for Cdk2 but not Cdk4. In pRB-deficient cells,
      phosphorylation of PP1alpha occurred in M-phase but not at G(1)/S. G(1)/S
      phosphorylation was at least partially restored after reintroduction of pRB into 
      these cells. Consistent with this result, PP1alpha phosphorylated at Thr-320
      co-precipitated with pRB during G(1)/S but was found in extracts immunodepleted
      of pRB in M-phase. In conjunction with earlier studies, these results indicate
      that PP1alpha may control pRB function throughout the cell cycle. In addition,
      our new results suggest that different subpopulations of PP1alpha regulate the
      G(1)/S and G(2)/M transitions and that PP1alpha complexed to pRB requires
      inhibitory phosphorylation by G(1)-specific Cdks in order to prevent untimely
      reactivation of pRB and permit transition from G(1)- to S-phase and/or complete
      S-phase.
FAU - Liu, C W
AU  - Liu CW
AD  - Division of Hematology/Oncology, Childrens Hospital Los Angeles, University of
      Southern California School of Medicine, Los Angeles, California 90027, USA.
FAU - Wang, R H
AU  - Wang RH
FAU - Dohadwala, M
AU  - Dohadwala M
FAU - Schonthal, A H
AU  - Schonthal AH
FAU - Villa-Moruzzi, E
AU  - Villa-Moruzzi E
FAU - Berndt, N
AU  - Berndt N
LA  - eng
GR  - 1112/Telethon/Italy
GR  - CA-54167/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 1114-81-4 (Phosphothreonine)
RN  - 6A839B2HYS (olomoucine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - P39Y9652YJ (Kinetin)
SB  - IM
MH  - *CDC2-CDC28 Kinases
MH  - *Cell Cycle
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - G1 Phase
MH  - Humans
MH  - Immunoblotting
MH  - Kinetin
MH  - Phosphoprotein Phosphatases/antagonists & inhibitors/*metabolism
MH  - Phosphorylation
MH  - Phosphothreonine/metabolism
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Purines/pharmacology
MH  - Recombinant Proteins/metabolism
MH  - Retinoblastoma Protein/metabolism
MH  - S Phase
MH  - Tumor Cells, Cultured
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - 10.1074/jbc.274.41.29470 [doi]
AID - S0021-9258(19)51996-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 8;274(41):29470-5. doi: 10.1074/jbc.274.41.29470.