PMID- 10318862
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 20
DP  - 1999 May 14
TI  - A protein phosphatase methylesterase (PME-1) is one of several novel proteins 
      stably associating with two inactive mutants of protein phosphatase 2A.
PG  - 14382-91
AB  - Carboxymethylation of proteins is a highly conserved means of regulation in 
      eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is 
      reversibly methylated at its carboxyl terminus by specific methyltransferase and 
      methylesterase enzymes which have been purified, but not cloned. 
      Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, 
      we report that substitution of glutamine for either of two putative active site 
      histidines in the PP2A C subunit results in inactivation of PP2A and formation of 
      stable complexes between PP2A and several cellular proteins. One of these 
      cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was 
      purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from 
      yeast to human and contains a motif found in lipases having a catalytic 
      triad-activated serine as their active site nucleophile. Bacterially expressed 
      PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor 
      of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 
      represents the first mammalian protein methylesterase to be cloned. Several lines 
      of evidence indicate that, although there appears to be a role for C subunit 
      carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at 
      the extreme carboxyl terminus of the C subunit also play an important role in 
      PME-1 binding to a catalytically inactive mutant.
FAU - Ogris, E
AU  - Ogris E
AD  - Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute and 
      Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Du, X
AU  - Du X
FAU - Nelson, K C
AU  - Nelson KC
FAU - Mak, E K
AU  - Mak EK
FAU - Yu, X X
AU  - Yu XX
FAU - Lane, W S
AU  - Lane WS
FAU - Pallas, D C
AU  - Pallas DC
LA  - eng
SI  - GENBANK/AF157028
GR  - R01 CA057327/CA/NCI NIH HHS/United States
GR  - CA57327/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 (DNA, Complementary)
RN  - 0 (Enzyme Inhibitors)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
RN  - EC 3.1.1.- (protein phosphatase methylesterase-1)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carboxylic Ester Hydrolases/chemistry/isolation & purification/*metabolism
MH  - Catalytic Domain
MH  - Cloning, Molecular
MH  - DNA, Complementary/chemistry
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Mutagenesis, Site-Directed
MH  - Okadaic Acid/pharmacology
MH  - Phosphoprotein Phosphatases/*genetics/*metabolism
MH  - Protein Phosphatase 2
MH  - Structure-Activity Relationship
MH  - Yeasts
PMC - PMC3503312
MID - NIHMS420948
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - S0021-9258(19)73314-6 [pii]
AID - 10.1074/jbc.274.20.14382 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):14382-91. doi: 10.1074/jbc.274.20.14382.