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J. Cell Biol.,
Volume 140, Number 5, March 9, 1998 1113-1124


* Department of Molecular Biology, Muscle cells are frequently subjected to severe conditions caused by heat, oxidative, and mechanical stresses. The small heat shock proteins (sHSPs)
such as
The First and § Second Departments of Internal Medicine, Yokohama City University
School of Medicine, Kanazawa-ku, Yokohama 236, Japan;
Institute of Molecular and Cellular Biosciences, the University of
Tokyo, Tokyo 113, Japan; and ¶ National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira,
Tokyo 187, Japan
B-crystallin and HSP27, which are highly expressed in muscle cells, have been suggested to play roles in maintaining myofibrillar integrity against such
stresses. Here, we identified a novel member of the
sHSP family that associates specifically with myotonic
dystrophy protein kinase (DMPK). This DMPK-binding protein, MKBP, shows a unique nature compared
with other known sHSPs: (a) In muscle cytosol, MKBP
exists as an oligomeric complex separate from the complex formed by
B-crystallin and HSP27. (b) The expression of MKBP is not induced by heat shock, although it shows the characteristic early response of
redistribution to the insoluble fraction like other
sHSPs. Immunohistochemical analysis of skeletal muscle cells shows that MKBP localizes to the cross sections of individual myofibrils at the Z-membrane as
well as the neuromuscular junction, where DMPK has
been suggested to be concentrated. In vitro, MKBP enhances the kinase activity of DMPK and protects it
from heat-induced inactivation. These results suggest
that MKBP constitutes a novel stress-responsive system
independent of other known sHSPs in muscle cells and
that DMPK may be involved in this system by being
activated by MKBP. Importantly, since the amount of
MKBP protein, but not that of other sHSP family
member proteins, is selectively upregulated in skeletal
muscle from DM patients, an interaction between
DMPK and MKBP may be involved in the pathogenesis of DM.
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