PMID- 10409661
OWN - NLM
STAT- MEDLINE
DCOM- 19990826
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 30
DP  - 1999 Jul 23
TI  - Abnormal cardiac structure and function in mice expressing nonphosphorylatable
      cardiac regulatory myosin light chain 2.
PG  - 21085-94
AB  - A role for myosin phosphorylation in modulating normal cardiac function has long 
      been suspected, and we hypothesized that changing the phosphorylation status of a
      cardiac myosin light chain might alter cardiac function in the whole animal. To
      test this directly, transgenic mice were created in which three potentially
      phosphorylatable serines in the ventricular isoform of the regulatory myosin
      light chain were mutated to alanines. Lines were obtained in which replacement of
      the endogenous species in the ventricle with the nonphosphorylatable,
      transgenically encoded protein was essentially complete. The mice show a spectrum
      of cardiovascular changes. As previously observed in skeletal muscle, Ca(2+)
      sensitivity of force development was dependent upon the phosphorylation status of
      the regulatory light chain. Structural abnormalities were detected by both gross 
      histology and transmission electron microscopic analyses. Mature animals showed
      both atrial hypertrophy and dilatation. Echocardiographic analysis revealed that 
      as a result of chamber enlargement, severe tricuspid valve insufficiency resulted
      in a detectable regurgitation jet. We conclude that regulated phosphorylation of 
      the regulatory myosin light chains appears to play an important role in
      maintaining normal cardiac function over the lifetime of the animal.
FAU - Sanbe, A
AU  - Sanbe A
AD  - Department of Pediatrics, Division of Molecular Cardiovascular Biology,
      Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
FAU - Fewell, J G
AU  - Fewell JG
FAU - Gulick, J
AU  - Gulick J
FAU - Osinska, H
AU  - Osinska H
FAU - Lorenz, J
AU  - Lorenz J
FAU - Hall, D G
AU  - Hall DG
FAU - Murray, L A
AU  - Murray LA
FAU - Kimball, T R
AU  - Kimball TR
FAU - Witt, S A
AU  - Witt SA
FAU - Robbins, J
AU  - Robbins J
LA  - eng
GR  - HL41496/HL/NHLBI NIH HHS/United States
GR  - HL56370/HL/NHLBI NIH HHS/United States
GR  - HL56620/HL/NHLBI NIH HHS/United States
GR  - etc.
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 (Myosin Light Chains)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Heart/*physiopathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron
MH  - Molecular Sequence Data
MH  - Myocardium/*metabolism/pathology/ultrastructure
MH  - Myosin Light Chains/genetics/*metabolism
MH  - Phosphorylation
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - 10.1074/jbc.274.30.21085 [doi]
AID - S0021-9258(19)72550-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 23;274(30):21085-94. doi: 10.1074/jbc.274.30.21085.