PMID- 10606530
OWN - NLM
STAT- MEDLINE
DCOM- 20000119
LR  - 20191210
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 38
IP  - 51
DP  - 1999 Dec 21
TI  - A novel phosphoprotein inhibitor of protein type-1 phosphatase holoenzymes.
PG  - 16952-7
AB  - Control of protein phosphatases is now understood to depend on binding to a
      variety of regulatory or targeting subunits to form holoenzymes with restricted
      localization and substrate specificity. In addition, the catalytic subunits of
      both type-1 and type-2 phosphatases bind specific inhibitor proteins. Here, we
      report discovery of a new inhibitor protein called PHI-1 that is specific for
      type-1 protein phosphatase (PP1). Recombinant tagged PHI-1 was phosphorylated by 
      protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced 
      inhibitory potency 50-fold. Mutation of Thr57 to Ala gave a protein
      phosphorylated only on Ser, without change in inhibitory activity, indicating
      that phosphorylation of Thr57 was required for full activity. Immunoblotting
      showed that PHI-1 was expressed in most animal tissues and several cell lines,
      and a second larger protein called PHI-2 was present in different muscles,
      especially cardiac muscle. Unlike any other known inhibitor, PHI-1 inhibited the 
      myosin- and glycogen-associated holoenzyme versions of PP1 as well as the
      monomeric catalytic subunit of PP1. Discovery of PHI-1 and PHI-2 opens new
      possibilities for regulation of PP1 via phosphorylation-dependent signaling
      pathways.
FAU - Eto, M
AU  - Eto M
AD  - Center for Cell Signaling, University of Virginia School of Medicine,
      Charlottesville 22908, USA.
FAU - Karginov, A
AU  - Karginov A
FAU - Brautigan, D L
AU  - Brautigan DL
LA  - eng
GR  - GM-56362/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Holoenzymes)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (PPP1R14A protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ppp1r14a protein, mouse)
RN  - 0 (Ppp1r14a protein, rat)
RN  - 0 (Ppp1r14b protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (phosphoprotein phosphatase inhibitor 1)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Enzyme Inhibitors/*chemistry/isolation & purification
MH  - Holoenzymes/chemistry
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Muscle Proteins/chemistry/genetics
MH  - Phosphoprotein Phosphatases/*antagonists & inhibitors
MH  - Phosphoproteins/biosynthesis/*chemistry/isolation & purification
MH  - Protein Biosynthesis
MH  - Protein Phosphatase 1
MH  - Proteins/*chemistry/genetics/isolation & purification
MH  - Rats
MH  - Recombinant Fusion Proteins/biosynthesis/isolation & purification
MH  - Sequence Homology, Amino Acid
MH  - Swine
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - bi992030o [pii]
AID - 10.1021/bi992030o [doi]
PST - ppublish
SO  - Biochemistry. 1999 Dec 21;38(51):16952-7. doi: 10.1021/bi992030o.