PMID- 16920702
OWN - NLM
STAT- MEDLINE
DCOM- 20061206
LR  - 20210212
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 42
DP  - 2006 Oct 20
TI  - Phosphorylation of myosin phosphatase targeting subunit 3 (MYPT3) and regulation 
      of protein phosphatase 1 by protein kinase A.
PG  - 31202-11
AB  - Myosin phosphatase targeting subunit 3 (MYPT3) and transforming growth 
      factor-beta-inhibited membrane-associated protein (TIMAP) are two closely related 
      myosin-binding targeting subunits of protein phosphatase 1 (PP1c) with a 
      characteristic CAAX (where AA indicates aliphatic amino acid) box at the C 
      termini. Here we show that MYPT3 can be a substrate for protein kinase A (PKA). 
      We first mapped the multiple phosphorylation sites within a central conserved 
      motif. Deletion or mutations of this motif resulted in enhancement of the 
      associated PP1c activity, suggesting that phosphorylation of MYPT3 may play an 
      important role in regulating PP1c catalytic activity. However, unlike the other 
      known MYPTs, which upon phosphorylation inhibit PP1c, PKA phosphorylation of 
      MYPT3 resulted in PP1c activation, indicating a different mode of action. There 
      is a direct interaction between the central conserved phosphorylated site motif 
      with the N-terminal ankyrin repeat region; this interaction was significantly 
      reduced with MYPT3 phosphorylation or acidic phosphorylation site mutations, with 
      concomitant alterations in biochemical and morphological consequences. We 
      therefore propose a novel mechanism for the phosphorylation of MYPT3 by PKA and 
      activation of the catalytic activity through direct interaction of a central 
      region of MYPT3 with its N-terminal region.
FAU - Yong, Jeffery
AU  - Yong J
AD  - GSK-IMCB Group, Institute of Molecular and Cell Biology, Singapore 138673, 
      Singapore.
FAU - Tan, Ivan
AU  - Tan I
FAU - Lim, Louis
AU  - Lim L
FAU - Leung, Thomas
AU  - Leung T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060818
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (PPP1R16A protein, human)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.53 (Myosin-Light-Chain Phosphatase)
RN  - EC 3.4.21.4 (Trypsin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/chemistry/*physiology
MH  - Chlorocebus aethiops
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism/*physiology
MH  - *Gene Expression Regulation, Enzymologic
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Proteins/chemistry/*physiology
MH  - Molecular Sequence Data
MH  - Myosin-Light-Chain Phosphatase/*chemistry/metabolism
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphorylation
MH  - Protein Phosphatase 1
MH  - Sequence Homology, Amino Acid
MH  - Trypsin/chemistry
EDAT- 2006/08/22 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/08/22 09:00
PHST- 2006/08/22 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/08/22 09:00 [entrez]
AID - S0021-9258(19)84033-4 [pii]
AID - 10.1074/jbc.M607287200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Oct 20;281(42):31202-11. doi: 10.1074/jbc.M607287200. Epub 2006 
      Aug 18.